Affinage · Plasmodium

MSP1

PF3D7_0930300 · merozoite surface protein 1

Annotated
2026-09-08
96 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MSP1 (PF3D7_0930300) is the principal GPI-anchored surface protein of the Plasmodium merozoite and functions as a stage-transiting adhesin that mediates both host erythrocyte rupture during egress and initial attachment during invasion (PMID:2995820, PMID:26468747, PMID:25778531). It is synthesized as a ~195 kDa precursor that is proteolytically matured into a non-covalent surface complex of ~83, ~42, and ~19 kDa fragments (PMID:2995820), with the intact protein attached to the merozoite membrane through a structurally distinctive GPI anchor bearing an extra mannose and myristate/palmitate acylation (PMID:8992312). Two sequential proteases act on MSP1: PfSUB1, discharged into the parasitophorous vacuole just before egress, matures the surface complex, and its inhibition leaves unprocessed MSP1 on the surface and blocks invasion (PMID:19214190); the SUB1-processed form gains the capacity to bind erythrocyte spectrin, and parasites with inefficiently processed or surface-depleted MSP1 show severe egress defects, establishing that processed MSP1 drives host cell rupture (PMID:26468747). During the subsequent invasion, the micronemal sheddase PfSUB2 removes the ectodomain, retaining only the C-terminal MSP1(19) fragment on the parasite (PMID:16322767). MSP1 engages host receptors through distinct regions: the N-terminus binds glycophorin A, whose GPA-band 3 complex is essential for infection in vivo (PMID:25778531), while the C-terminal MSP1(42)/MSP1(19) products bind nonglycosylated exofacial regions of erythrocyte band 3 (PMID:12692305); MSP1(42) additionally binds heparin-like molecules (PMID:20220119). The retained MSP1(19) fragment is a compact two-EGF-domain module with a U-shaped interdomain interface stabilized by disulfide bonds, structurally positioning the N-terminal processing site near the GPI anchor and carrying the epitopes of invasion-inhibitory antibodies (PMID:10339410, PMID:1775158); its disulfide-bonded conformation is absolutely required for protective immunogenicity (PMID:8015856). On the merozoite surface, MSP1 nucleates multiple independent complexes by binding peripheral partners including MSP6, MSP7, MSP3, MSPDBL1, and MSPDBL2 (MSP6 contacting the p38 subunit and MSP7 contacting p83/p30/p38), all of which contribute to erythrocyte binding (PMID:11166390, PMID:16940297, PMID:26823464). Beyond blood-stage invasion, MSP1 also functions in liver-stage development, where conditional silencing in P. berghei impairs hepatic merozoite formation (PMID:19380117), and after invasion MSP1(19) is internalized to mark food vacuole biogenesis (PMID:18769730).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1985 High

    Establishing that MSP1 is a large precursor cleaved into defined fragments framed the entire model of a proteolytically matured surface protein.

    Evidence Molecular cloning and sequencing of cDNA/genomic DNA with protein biochemistry defining the ~195 kDa precursor and its ~83/~42/~19 kDa products

    PMID:2995820

    Open questions at the time
    • Did not identify the proteases responsible for processing
    • Did not establish receptor-binding function of the fragments
  2. 1990 High

    Showing that only a small C-terminal fragment is carried into the new red cell and that antibodies to it block invasion pinpointed MSP1(19) as the functionally critical invasion moiety.

    Evidence Biochemical fractionation of merozoite surface proteins combined with antibody invasion-inhibition assays

    PMID:1694225

    Open questions at the time
    • Mechanism by which the fragment supports invasion was unresolved
    • Host receptor unknown at this point
  3. 1991 High

    Defining the C-terminal fragment as two EGF-like domains and locating fragment boundaries by N-terminal sequencing established the domain architecture of the retained module.

    Evidence N-terminal amino acid sequencing of purified fragments compared with predicted gene sequence; glycosylation analysis

    PMID:1775158

    Open questions at the time
    • 3D fold not yet determined
    • Functional role of the EGF domains unproven
  4. 1993 High

    Immunization with disulfide-bonded C-terminal EGF domains conferred protection that was abolished by reduction/alkylation, proving the conformation is essential for protective immunity.

    Evidence Recombinant P. yoelii MSP1 immunization with chemical reduction/alkylation and lethal blood-stage challenge in mice

    PMID:8015856

    Open questions at the time
    • Shown in P. yoelii, not P. falciparum
    • Does not define the protective epitopes at residue level
  5. 1996 High

    Characterizing the GPI anchor established how MSP1 is tethered to the merozoite membrane, a prerequisite for surface retention and shedding.

    Evidence Metabolic labeling and enzymatic/chemical structural analysis of the released GPI anchor

    PMID:8992312

    Open questions at the time
    • Did not address the sheddase that releases the ectodomain
    • Functional consequence of the atypical acylation not tested
  6. 1999 High

    Solving the MSP1(19) solution structure revealed a U-shaped two-EGF module placing the processing site near the GPI anchor and mapped inhibitory/blocking antibody epitopes onto the fold.

    Evidence NMR spectroscopy of 13C/15N-labelled recombinant protein with epitope mapping

    PMID:10339410

    Open questions at the time
    • Structure of the full processed complex not resolved
    • Receptor-binding surface not yet mapped
  7. 2001 High

    Fine mutagenesis and PEPSCAN localized conformational invasion-inhibitory epitopes to the first EGF domain and enabled design of proteins discriminating inhibitory from blocking antibodies, clarifying the antigenic determinants relevant to vaccine design.

    Evidence Site-directed mutagenesis (26 mutants), PEPSCAN, BIAcore, and 3D structural mapping

    PMID:11292349

    Open questions at the time
    • Does not establish the natural receptor contacts of these residues
    • Blocking-antibody interference mechanism not fully resolved
  8. 2001 Medium

    Identifying MSP6 as a non-covalent partner of MSP1 opened the concept that MSP1 organizes accessory surface proteins into a complex.

    Evidence Co-immunoprecipitation from culture supernatant with N-terminal sequencing, MS, and immunofluorescence

    PMID:11166390

    Open questions at the time
    • Single Co-IP; binding subunit inferred not directly mapped
    • Fraction of MSP6 unbound to MSP1 unexplained
  9. 1994 Medium

    Demonstrating disulfide-dependent authentic folding of recombinant MSP1(19) in yeast, and that a single E-to-Q change alters conformation, established requirements for producing correctly folded antigen.

    Evidence Yeast expression of MSP1(19) variants with direct/competitive ELISA and conformational analysis

    PMID:7516493

    Open questions at the time
    • Two-assay single-lab characterization
    • In vivo protective consequence of the E-to-Q change not tested
  10. 2003 High

    Identifying erythrocyte band 3 regions 5ABC and 6A as receptors for the C-terminal MSP1 products defined the host-binding function of MSP1(42)/MSP1(19).

    Evidence Pulldown binding assays with recombinant fragments and band 3 peptides, enzymatic RBC treatments, and invasion inhibition

    PMID:12692305

    Open questions at the time
    • Affinity and stoichiometry of the interaction not quantified
    • Relationship to the N-terminal GPA interaction unresolved at this stage
  11. 2003 Medium

    Showing MSP1(42) and MSP9 form a co-ligand complex targeting band 3 extended the invasion adhesion model to multi-protein receptor engagement.

    Evidence Co-immunoprecipitation, pulldown binding assays with recombinant MSP9, and invasion inhibition

    PMID:14630931

    Open questions at the time
    • Single lab; in vivo requirement of the co-complex not tested
    • Whether MSP9 binds MSP1 directly or via band 3 not fully separated
  12. 2003 High

    A crystal structure of MSP1(19) with a non-inhibitory Fab distinguished antibody binding from functional inhibition, showing surface binding alone does not block invasion.

    Evidence X-ray crystallography of MSP1(19)-Fab complex, immunofluorescence, and invasion inhibition assay

    PMID:12729744

    Open questions at the time
    • Does not explain why some epitopes inhibit and others do not mechanistically
  13. 2005 High

    Identifying PfSUB2 as the micronemal sheddase that removes the MSP1 ectodomain during invasion defined the enzyme responsible for retaining only MSP1(19).

    Evidence Molecular identification, propeptide binding/inhibition, actin-dependence, and immunolocalization

    PMID:16322767

    Open questions at the time
    • Exact MSP1 cleavage site by PfSUB2 not defined here
    • Consequence of blocking shedding on invasion kinetics not fully quantified
  14. 2006 High

    Reconstituting MSP6 and MSP7 binding to specific MSP1 subunits with recombinant proteins mapped the architecture of the surface complex and showed only processed MSP1 binds MSP6.

    Evidence In vitro binding with recombinant MSP1 subunits, MSP6, and MSP7, deletion analysis, and analytical ultracentrifugation

    PMID:16940297

    Open questions at the time
    • In vitro reconstitution; native surface stoichiometry not measured
    • Functional role of MSP6 multimerization unresolved
  15. 2008 High

    Tracking MSP1(19) after invasion showed it is internalized and marks food vacuole biogenesis, revealing a post-invasion fate distinct from its surface role.

    Evidence Metabolic labeling, live fluorescence imaging, immuno-EM, and vacuole fractionation

    PMID:18769730

    Open questions at the time
    • Functional contribution of MSP1(19) to food vacuole formation not established
    • Mechanism of endocytic uptake unknown
  16. 2009 High

    Establishing PfSUB1 as the pre-egress protease that matures MSP1 completed the two-protease processing scheme and linked processing to invasion competence.

    Evidence PfSUB1 inhibitor treatment with Western blot of MSP1 processing and invasion assays

    PMID:19214190

    Open questions at the time
    • Direct enzyme-substrate reconstitution not shown here
    • Contribution of MSP6/MSP7 co-processing to invasion not dissected
  17. 2009 High

    Conditional silencing in P. berghei revealed MSP1 is required for liver-stage merozoite formation, extending its role beyond the blood stage.

    Evidence Flp/FRT conditional gene silencing in sporozoites with liver-stage development assays

    PMID:19380117

    Open questions at the time
    • Shown in P. berghei, not P. falciparum
    • Molecular function of MSP1 in the liver stage undefined
  18. 2010 Medium

    Demonstrating that MSP1(42) and MSP1(33), but not MSP1(19), bind sulfated heparin-like molecules identified an additional carbohydrate interaction relevant to invasion inhibition.

    Evidence Heparin-binding assays with native and recombinant fragments and real-time invasion imaging

    PMID:20220119

    Open questions at the time
    • Single lab; physiological heparan sulfate ligand on RBCs not identified
    • Relationship to band 3/GPA binding unresolved
  19. 2015 High

    Showing that SUB1 processing activates spectrin binding and that MSP1 loss/impaired processing causes egress defects reframed MSP1 as an active mediator of host cell rupture, not merely an invasion adhesin.

    Evidence MSP1 processing mutants, spectrin-binding assays, live egress imaging, and surface-MSP1 displacement with secondary structure analysis

    PMID:26468747

    Open questions at the time
    • How spectrin binding mechanically destabilizes the membrane not defined
    • Whether partner proteins modulate spectrin binding untested
  20. 2015 High

    Identifying the MSP1 N-terminus as a glycophorin A binding domain and showing GPA-band 3 knockout mice resist malaria established the in vivo essentiality of the MSP1-GPA-band 3 adhesion axis.

    Evidence Phage display mapping, recombinant binding assays, GPA-band 3 knockout mouse model, and in vivo infection challenge

    PMID:25778531

    Open questions at the time
    • Mouse model reports the receptor complex, not direct MSP1 gene knockout in vivo
    • Sequential order of GPA vs band 3 engagement not resolved
  21. 2016 High

    Systematic reconstitution showed MSP3, MSP6, MSPDBL1, MSPDBL2, and MSP7 each bind MSP1 independently to form multiple overlapping erythrocyte-binding complexes, and anti-p83 antibodies inhibit all forms, defining MSP1 as a hub organizing redundant surface complexes.

    Evidence Direct recombinant binding assays, erythrocyte binding assays, and growth inhibition with anti-p83 antibodies

    PMID:26823464

    Open questions at the time
    • Relative abundance of each complex form on the native surface not quantified
    • Functional redundancy not tested by combined gene disruption

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the processed MSP1 complex integrates its egress-promoting spectrin interaction with its multiple invasion-adhesion contacts (GPA, band 3, heparin) into a single ordered mechanochemical program, and the molecular function of MSP1 in the liver stage, remain unresolved.
  • No structure of the full processed complex bound to receptors
  • Liver-stage molecular function of MSP1 undefined
  • Order and coordination of GPA/band 3/spectrin engagement unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
ERYTHROCYTE BAND 3 (REGIONS 5ABC AND 6A)ERYTHROCYTE GLYCOPHORIN AERYTHROCYTE SPECTRINHEPARIN-LIKE MOLECULESMSP3MSP6MSP7MSP9 (ABRA)MSPDBL1MSPDBL2PFSUB1 (MATURATION PROTEASE)PFSUB2 (SHEDDASE)
Complex memberships
MSP1 processed surface complex (p83/p30/p38/p42/p19)MSP1(42)-MSP9 co-ligand complexMSP1-MSP3 / MSP1-MSPDBL1 / MSP1-MSPDBL2 complexesMSP1-MSP6 complex (MSP6 binds p38)MSP1-MSP7 complex (MSP7 binds p83/p30/p38)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 During erythrocyte invasion by P. falciparum merozoites, only a small C-terminal fragment of the MSP1 precursor complex is retained on the parasite surface and carried into the newly infected red cell; antibodies to this fragment inhibit invasion. Biochemical fractionation of merozoite surface proteins combined with antibody invasion-inhibition assays The Journal of experimental medicine High 1694225
1985 MSP1 (P195) is synthesized as a ~195 kDa precursor that is proteolytically processed into three major merozoite surface fragments of ~83 kDa, ~42 kDa, and ~19 kDa; the complete gene structure was determined from cDNA and genomic DNA clones. Molecular cloning and sequencing of cDNA and genomic DNA; protein biochemistry Nature High 2995820
1991 The C-terminal fragment of MSP1 that is carried into the red cell during invasion consists of two epidermal growth factor (EGF)-like domains; N-terminal amino acid sequencing of fragments defined their position in the precursor. The smaller fragment is not N-glycosylated. A homologous cleavage sequence and EGF-like domain structure is found in MSP1 of other Plasmodium species. N-terminal amino acid sequencing of purified fragments; comparison with predicted gene sequence; glycosylation analysis Molecular and biochemical parasitology High 1775158
1996 MSP1 is anchored in the merozoite membrane via a glycosylphosphatidylinositol (GPI) anchor; detailed structural analysis showed the GPI anchor contains an extra α1-2 linked mannose at the conserved trimannosyl core glycan and carries primarily myristic acid at the inositol ring with palmitic acid in ester linkage on diacylglycerol. Metabolic labeling with tritiated precursors; enzymatic and chemical treatments; structural analysis of released GPI anchor fragments Molecular and biochemical parasitology High 8992312
1997 Monoclonal antibodies that inhibit MSP1 secondary processing and erythrocyte invasion are blocked by naturally acquired human antibodies specific for epitopes within the N-terminal 83 kDa domain of MSP1, completely abrogating the invasion-inhibitory effect; blocking antibodies compete with processing-inhibitory antibodies for binding to MSP1(19) epitopes on the merozoite surface. Quantitative antibody-mediated inhibition assays; competitive binding assays; affinity-purified human antibodies tested in invasion inhibition and MSP1 secondary processing assays in vitro The Journal of experimental medicine High 9362529
1999 The solution structure of the 96-residue C-terminal MSP1(19) fragment was determined by NMR; it comprises two EGF-like domains with a novel U-shaped interdomain interface formed by a hydrophobic residue cluster, placing the N-terminal proteolytic processing site close to the C-terminal GPI anchor site, consistent with a membrane-bound proteinase mediating processing during erythrocyte invasion. Epitopes for invasion-inhibitory and blocking antibodies were mapped onto the 3D structure. NMR spectroscopy on uniformly 13C/15N-labelled recombinant protein expressed in Pichia pastoris; structure determination and epitope mapping Journal of molecular biology High 10339410
2003 The crystal structure of recombinant P. falciparum MSP1(19) in complex with the Fab fragment of monoclonal antibody G17.12 was determined; G17.12 recognizes a discontinuous epitope of 13 residues on the first EGF-like domain of MSP1(19). G17.12 binds uniformly to the surface of merozoites from late schizont stage but does not inhibit erythrocyte invasion or MSP1 processing. X-ray crystallography of MSP1(19)-Fab complex; immunofluorescence on intact merozoites; invasion inhibition assay Journal of molecular biology High 12729744
2001 Epitopes for invasion-inhibitory mAbs 12.8 and 12.10 and blocking mAbs 1E1 and 7.5 on MSP1(19) were mapped by site-directed mutagenesis (26 individual amino acid changes) and PEPSCAN analysis; inhibitory epitopes are conformational and primarily within the first EGF-like domain; incorporation of specific amino acid changes enabled design of proteins that bound inhibitory but not blocking antibodies. Site-directed mutagenesis; PEPSCAN; Western blotting; BIAcore binding analysis; 3D structural mapping Journal of molecular biology High 11292349
2003 Two nonglycosylated exofacial regions of erythrocyte band 3 (termed 5ABC and 6A) serve as host receptors binding the C-terminal processing products of MSP1. Native MSP1(42) and recombinant MSP1(19) both bound 5ABC; MSP1(42) also bound intact RBCs; binding was sialic acid-independent but chymotrypsin-sensitive. Band 3-derived peptides and soluble 5ABC inhibited P. falciparum invasion of RBCs in vitro. Pulldown binding assays with recombinant MSP1 fragments and band 3 peptides; neuraminidase and chymotrypsin treatment of RBCs; in vitro invasion inhibition assays Proceedings of the National Academy of Sciences of the United States of America High 12692305
2003 MSP1(42) and MSP9 (ABRA) form a stable co-ligand complex that together targets erythrocyte band 3 receptor (5ABC) during invasion; MSP9 also binds 5ABC and intact erythrocytes independently, and soluble 5ABC blocks MSP9-erythrocyte binding. Co-immunoprecipitation; pulldown binding assays with recombinant MSP9 polypeptides; invasion inhibition assays The Journal of biological chemistry Medium 14630931
2005 PfSUB2, an integral membrane subtilisin-like protease stored in micronemes, is the merozoite surface 'sheddase' responsible for shedding MSP1 ectodomain components during erythrocyte invasion. PfSUB2 is secreted onto the parasite surface upon merozoite release and translocates to the posterior pole in an actin-dependent manner. The recombinant PfSUB2 propeptide binds specifically to mature parasite-derived PfSUB2 and potently and selectively inhibits MSP1 (and AMA1) shedding. Molecular identification of PfSUB2; propeptide binding assay (pulldown); selective inhibition of MSP1 shedding in parasite cultures; actin inhibitor treatment; immunolocalization PLoS pathogens High 16322767
2009 PfSUB1, a subtilisin-like protease discharged into the parasitophorous vacuole, proteolytically matures MSP1 (as well as MSP6 and MSP7) on the merozoite surface just before egress. Inhibition of PfSUB1 activity results in accumulation of unprocessed MSP1 on the merozoite surface and significantly reduces erythrocyte invasion. PfSUB1 inhibitor treatment of P. falciparum cultures; Western blot analysis of MSP1 processing; invasion assay The EMBO journal High 19214190
2009 MSP1 is expressed during liver-stage as well as blood-stage schizogony in P. berghei. Conditional silencing of MSP1 in sporozoites using a Flp/FRT recombination system impaired subsequent merozoite formation in the liver, demonstrating a dual role for MSP1 in both liver-stage and erythrocytic-stage parasite development. Flp/FRT conditional gene silencing in P. berghei; sporozoite-stage promoter-driven excision; liver-stage development assay Cell host & microbe High 19380117
2010 MSP1(42), a processed form of MSP1 involved in invasion, binds heparin-like molecules in a specific manner; MSP1(33) also binds heparin, but MSP1(19) does not. Optimal heparin binding and invasion inhibition required a degree of sulfation ≥2, disulfation of N-acetylglucosamine or hexuronic acid, and a minimum chain length of 6 monosaccharides. Heparin-binding assays with native MSP1(42) and recombinant fragments; real-time imaging of invasion inhibition; structure-activity analysis of heparin variants Blood Medium 20220119
2015 SUB1-mediated proteolytic processing of MSP1 modifies its secondary structure and activates its capacity to bind spectrin, the major component of the erythrocyte cytoskeleton. Parasites expressing an inefficiently processed MSP1 mutant showed delayed egress, and merozoites lacking surface-bound MSP1 displayed a severe egress defect, indicating that processed MSP1 facilitates host erythrocyte rupture for parasite egress. MSP1 processing mutant parasites; spectrin-binding assays; live egress imaging; genetic knock-down/displacement of surface MSP1; secondary structure analysis Cell host & microbe High 26468747
2015 The amino-terminus of MSP1 directly interacts with human erythrocyte glycophorin A (GPA). Phage display mapping identified the binding domain; this region of MSP1 potently inhibits P. falciparum invasion of RBCs. A genetically modified mouse model lacking the GPA-band 3 complex in RBCs was completely resistant to malaria infection in vivo, indicating an essential role of the MSP1-GPA-band 3 complex in initial adhesion during invasion. Phage display technology; recombinant protein binding assays; GPA-band 3 knockout mouse model; in vivo infection challenge Blood High 25778531
2001 MSP6 (36 kDa) is non-covalently associated with the MSP1 complex on the merozoite surface. MSP6(36) was co-immunoprecipitated with MSP1 from parasite culture supernatant. MSP6(36) is also found in a form not bound to MSP1. The C-terminal region of MSP6 may be involved in binding to MSP1 subunit p38. N-terminal sequencing; mass spectrometry; co-immunoprecipitation from culture supernatant; immunofluorescence; gene cloning Molecular and biochemical parasitology Medium 11166390
2006 Using heterologously produced recombinant proteins, MSP6(36) and MSP7 each bind independently to MSP1. MSP6(36) contacts only the p38 subunit of MSP1, while MSP7 interacts with p83, p30, and p38. The intact C-terminal region of MSP6 is required for association with p38 and for MSP6 multimerization into tetramers. Only the processed (not precursor) form of MSP1 interacts with MSP6(36). In vitro binding assays with recombinant MSP1 subunits, MSP6, and MSP7; deletion/truncation analysis of MSP6; analytical ultracentrifugation for multimerization The Journal of biological chemistry High 16940297
2016 MSP3, MSP6, MSPDBL1, MSPDBL2, and MSP7 each bind directly to MSP1, but independently of each other, forming multiple distinct MSP1 complex forms on the parasite surface. These MSP1 complexes have overlapping functions and interact directly with human erythrocytes. Inhibitory antibodies targeting the p83 fragment of MSP1 inhibit all forms of MSP1 complexes and disrupt parasite growth in vitro. Direct binding assays between recombinant proteins; erythrocyte binding assays; parasite growth inhibition with anti-p83 antibodies The Journal of biological chemistry High 26823464
2008 After merozoite invasion, MSP1(19) persists intact throughout the intraerythrocytic cycle and is the first marker for food vacuole biogenesis. MSP1(19) is rapidly endocytosed into small vacuoles in the ring stage, which coalesce to form the single food vacuole containing hemozoin; it persists in the residual body. MSP1(19) and the chloroquine resistance transporter (CRT) are both components of the food vacuole membrane. Newly synthesized MSP1 is excluded from the vacuole. Metabolic labeling of MSP1(19); fluorescence live imaging; immuno-electron microscopy; immunochemical analysis of vacuole fractions PloS one High 18769730
1994 Recombinant MSP1(19) C-terminal EGF-like domain fragment expressed in yeast displays correct disulfide bond-dependent conformation; structural analysis showed a single amino acid change (E to Q) in the first EGF domain significantly alters conformation. Conserved and variant B-cell epitopes including known protective antibody targets were authentically recreated. Yeast expression and secretion of His-tagged recombinant MSP1(19) variants; direct and competitive ELISA; disulfide bond-dependent conformational analysis Molecular and biochemical parasitology Medium 7516493
1993 Immunization of mice with a recombinant P. yoelii MSP1 protein containing only the two C-terminal EGF-like domains confers protection against lethal blood-stage challenge; reduction and alkylation of the protein (disrupting disulfide bonds) abolished protection, demonstrating an absolute requirement for the disulfide-bonded conformation for immunogenicity and protective efficacy. Recombinant protein immunization; chemical reduction and alkylation; lethal blood-stage challenge model in mice Parasite immunology High 8015856

Source papers

Stage 0 corpus · 96 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 A single fragment of a malaria merozoite surface protein remains on the parasite during red cell invasion and is the target of invasion-inhibiting antibodies. The Journal of experimental medicine 494 1694225
1999 Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Transactions of the Royal Society of Tropical Medicine and Hygiene 461 10674079
1993 Analysis of sequence diversity in the Plasmodium falciparum merozoite surface protein-1 (MSP-1). Molecular and biochemical parasitology 339 8515771
1985 Primary structure of the precursor to the three major surface antigens of Plasmodium falciparum merozoites. Nature 285 2995820
1996 Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. The Journal of infectious diseases 272 8627050
1991 Proteolytic processing of the Plasmodium falciparum merozoite surface protein-1 produces a membrane-bound fragment containing two epidermal growth factor-like domains. Molecular and biochemical parasitology 234 1775158
1992 Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity. Parasite immunology 212 1625908
1997 Antibodies that inhibit malaria merozoite surface protein-1 processing and erythrocyte invasion are blocked by naturally acquired human antibodies. The Journal of experimental medicine 191 9362529
2003 Band 3 is a host receptor binding merozoite surface protein 1 during the Plasmodium falciparum invasion of erythrocytes. Proceedings of the National Academy of Sciences of the United States of America 178 12692305
1994 Immunization against malaria with a recombinant protein. Parasite immunology 178 8015856
1993 A recombinant 15-kilodalton carboxyl-terminal fragment of Plasmodium yoelii yoelii 17XL merozoite surface protein 1 induces a protective immune response in mice. Infection and immunity 177 8363656
2005 Molecular identification of a malaria merozoite surface sheddase. PLoS pathogens 173 16322767
1995 Immunogenicity and in vivo efficacy of recombinant Plasmodium falciparum merozoite surface protein-1 in Aotus monkeys. Molecular medicine (Cambridge, Mass.) 165 8529111
1996 Structural analysis of the glycosyl-phosphatidylinositol membrane anchor of the merozoite surface proteins-1 and -2 of Plasmodium falciparum. Molecular and biochemical parasitology 159 8992312
1992 A malaria merozoite surface protein (MSP1)-structure, processing and function. Memorias do Instituto Oswaldo Cruz 157 1343716
2010 Interactions with heparin-like molecules during erythrocyte invasion by Plasmodium falciparum merozoites. Blood 154 20220119
1999 Human antibodies to the 19kDa C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 inhibit parasite growth in vitro. Parasite immunology 145 10205793
2010 Genetic diversity among Plasmodium falciparum field isolates in Pakistan measured with PCR genotyping of the merozoite surface protein 1 and 2. Malaria journal 143 20043863
1995 Genotyping of Plasmodium falciparum isolates by the polymerase chain reaction and potential uses in epidemiological studies. Bulletin of the World Health Organization 141 7704931
2015 Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 Activates a Spectrin-Binding Function Enabling Parasite Egress from RBCs. Cell host & microbe 140 26468747
2002 Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus. Proceedings of the National Academy of Sciences of the United States of America 137 12466500
2011 Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen MSP1 in ChAd63 and MVA vaccine vectors. Molecular therapy : the journal of the American Society of Gene Therapy 134 21862998
1995 Serum antibodies from malaria-exposed people recognize conserved epitopes formed by the two epidermal growth factor motifs of MSP1(19), the carboxy-terminal fragment of the major merozoite surface protein of Plasmodium falciparum. Infection and immunity 133 7822010
1999 Solution structure of an EGF module pair from the Plasmodium falciparum merozoite surface protein 1. Journal of molecular biology 132 10339410
2005 Practical PCR genotyping protocols for Plasmodium vivax using Pvcs and Pvmsp1. Malaria journal 128 15854233
1999 Variation of Plasmodium falciparum msp1 block 2 and msp2 allele prevalence and of infection complexity in two neighbouring Senegalese villages with different transmission conditions. Transactions of the Royal Society of Tropical Medicine and Hygiene 127 10450422
2006 Immunity to recombinant plasmodium falciparum merozoite surface protein 1 (MSP1): protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity. Infection and immunity 123 16861644
2009 A multifunctional serine protease primes the malaria parasite for red blood cell invasion. The EMBO journal 122 19214190
1996 Identification of Plasmodium falciparum MSP-1 peptides able to bind to human red blood cells. Parasite immunology 122 9226689
1997 Acquired immune responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1 in individuals exposed to malaria. Infection and immunity 114 9125537
2001 Inhibitory and blocking monoclonal antibody epitopes on merozoite surface protein 1 of the malaria parasite Plasmodium falciparum. Journal of molecular biology 113 11292349
2011 Plasmodium falciparum msp1, msp2 and glurp allele frequency and diversity in sub-Saharan Africa. Malaria journal 112 21470428
1996 Natural immune response to the C-terminal 19-kilodalton domain of Plasmodium falciparum merozoite surface protein 1. Infection and immunity 110 8698500
2001 Efficacy of two alternate vaccines based on Plasmodium falciparum merozoite surface protein 1 in an Aotus challenge trial. Infection and immunity 108 11179324
2009 The carboxy-terminus of merozoite surface protein 1: structure, specific antibodies and immunity to malaria. Parasitology 106 19627632
2001 The merozoite surface protein 6 gene codes for a 36 kDa protein associated with the Plasmodium falciparum merozoite surface protein-1 complex. Molecular and biochemical parasitology 104 11166390
2003 Safety and immunogenicity of a three-component blood-stage malaria vaccine (MSP1, MSP2, RESA) against Plasmodium falciparum in Papua New Guinean children. Vaccine 103 14604568
1999 Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria. Parassitologia 102 10697894
2000 Plasmodium vivax synonymous substitution frequencies, evolution and population structure deduced from diversity in AMA 1 and MSP 1 genes. Molecular and biochemical parasitology 97 10802318
2009 Clonal conditional mutagenesis in malaria parasites. Cell host & microbe 95 19380117
2004 Fine specificity of serum antibodies to Plasmodium falciparum merozoite surface protein, PfMSP-1(19), predicts protection from malaria infection and high-density parasitemia. Infection and immunity 95 14977962
1997 Characterization of human T- and B-cell epitopes in the C terminus of Plasmodium falciparum merozoite surface protein 1: evidence for poor T-cell recognition of polypeptides with numerous disulfide bonds. Infection and immunity 93 9234749
2015 Recent advances in recombinant protein-based malaria vaccines. Vaccine 92 26458807
2000 Immunogenicity and efficacy in aotus monkeys of four recombinant Plasmodium falciparum vaccines in multiple adjuvant formulations based on the 19-kilodalton C terminus of merozoite surface protein 1. Infection and immunity 91 10722622
2003 A co-ligand complex anchors Plasmodium falciparum merozoites to the erythrocyte invasion receptor band 3. The Journal of biological chemistry 90 14630931
2007 Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. PLoS medicine 89 17355170
2004 Antibodies to the conserved C-terminal domain of the Plasmodium falciparum merozoite surface protein 1 and to the merozoite extract and their relationship with in vitro inhibitory antibodies and protection against clinical malaria in a Senegalese village. The Journal of infectious diseases 89 15609237
2002 Acquired immune responses to Plasmodium falciparum merozoite surface protein-1 in the human fetus. Journal of immunology (Baltimore, Md. : 1950) 86 11751981
2003 Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-1(42) malaria vaccine. Molecular and biochemical parasitology 84 12742586
2004 Antibodies to the N-terminal block 2 of Plasmodium falciparum merozoite surface protein 1 are associated with protection against clinical malaria. Infection and immunity 83 15501780
1994 Expression and antigenicity of Plasmodium falciparum major merozoite surface protein (MSP1(19)) variants secreted from Saccharomyces cerevisiae. Molecular and biochemical parasitology 83 7516493
2006 Genetic diversity of Plasmodium vivax in Kolkata, India. Malaria journal 82 16907979
1994 Purification of Plasmodium falciparum merozoites for analysis of the processing of merozoite surface protein-1. Methods in cell biology 82 7707987
2009 Strain-specific duffy binding protein antibodies correlate with protection against infection with homologous compared to heterologous plasmodium vivax strains in Papua New Guinean children. Infection and immunity 81 19564376
2003 Crystal structure of a Fab complex formed with PfMSP1-19, the C-terminal fragment of merozoite surface protein 1 from Plasmodium falciparum: a malaria vaccine candidate. Journal of molecular biology 80 12729744
1999 Longevity of naturally acquired antibody responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1. The American journal of tropical medicine and hygiene 80 10466961
2013 Natural acquisition of immunity to Plasmodium vivax: epidemiological observations and potential targets. Advances in parasitology 77 23384622
2009 Optimization and validation of multi-coloured capillary electrophoresis for genotyping of Plasmodium falciparum merozoite surface proteins (msp1 and 2). Malaria journal 77 19386138
2006 Urban malaria in Dakar, Senegal: chemosusceptibility and genetic diversity of Plasmodium falciparum isolates. The American journal of tropical medicine and hygiene 77 16837722
1993 A longitudinal study of naturally acquired cellular and humoral immune responses to a merozoite surface protein (MSP1) of Plasmodium falciparum in an area of seasonal malaria transmission. Parasite immunology 76 7877849
2015 Merozoite surface protein 1 recognition of host glycophorin A mediates malaria parasite invasion of red blood cells. Blood 75 25778531
2015 Using Amplicon Deep Sequencing to Detect Genetic Signatures of Plasmodium vivax Relapse. The Journal of infectious diseases 74 25748326
2008 Formation of the food vacuole in Plasmodium falciparum: a potential role for the 19 kDa fragment of merozoite surface protein 1 (MSP1(19)). PloS one 73 18769730
2006 Interactions between merozoite surface proteins 1, 6, and 7 of the malaria parasite Plasmodium falciparum. The Journal of biological chemistry 72 16940297
1999 Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1(19)) and T helper epitopes of tetanus toxoid. Vaccine 72 10519944
2011 Histidine affinity tags affect MSP1(42) structural stability and immunodominance in mice. Biotechnology journal 70 22076863
1997 Immunization with a recombinant C-terminal fragment of Plasmodium yoelii merozoite surface protein 1 protects mice against homologous but not heterologous P. yoelii sporozoite challenge. Infection and immunity 70 9353014
2006 Analysis of antibodies directed against merozoite surface protein 1 of the human malaria parasite Plasmodium falciparum. Infection and immunity 69 16428781
1998 Recombinant Mycobacterium bovis bacillus Calmette-Guérin secreting merozoite surface protein 1 (MSP1) induces protection against rodent malaria parasite infection depending on MSP1-stimulated interferon gamma and parasite-specific antibodies. The Journal of experimental medicine 68 9730886
2005 Antigenicity, immunogenicity, and protective efficacy of Plasmodium vivax MSP1 PV200l: a potential malaria vaccine subunit. The American journal of tropical medicine and hygiene 66 16291762
2008 Protection induced by Plasmodium falciparum MSP1(42) is strain-specific, antigen and adjuvant dependent, and correlates with antibody responses. PloS one 65 18665258
2002 Association of the IgG response to Plasmodium falciparum merozoite protein (C-terminal 19 kD) with clinical immunity to malaria in the Brazilian Amazon region. The American journal of tropical medicine and hygiene 65 12201577
2011 Genetic diversity of Plasmodium falciparum isolates from Pahang, Malaysia based on MSP-1 and MSP-2 genes. Parasites & vectors 64 22166488
2016 Multiple Plasmodium falciparum Merozoite Surface Protein 1 Complexes Mediate Merozoite Binding to Human Erythrocytes. The Journal of biological chemistry 61 26823464
2010 Naturally-acquired humoral immune responses against the N- and C-termini of the Plasmodium vivax MSP1 protein in endemic regions of Brazil and Papua New Guinea using a multiplex assay. Malaria journal 61 20092651
2010 Merozoite surface proteins of the malaria parasite: the MSP1 complex and the MSP7 family. International journal for parasitology 61 20451527
2003 Biochemical and immunological characterization of bacterially expressed and refolded Plasmodium falciparum 42-kilodalton C-terminal merozoite surface protein 1. Infection and immunity 61 14638762
2006 Genetic diversity in the Block 2 region of the merozoite surface protein 1 (MSP-1) of Plasmodium falciparum: additional complexity and selection and convergence in fragment size polymorphism. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 60 16517218
2018 Plasmodium falciparum msp1 and msp2 genetic diversity and allele frequencies in parasites isolated from symptomatic malaria patients in Bobo-Dioulasso, Burkina Faso. Parasites & vectors 59 29843783
2025 Molecular epidemiology and genetic diversity of disappearing Plasmodium vivax in southern Thailand. Scientific reports 5 39838039
2025 An mRNA Vaccine Expressing Blood-Stage Malaria Antigens Induces Complete Protection Against Lethal Plasmodium yoelii. Vaccines 5 40733679
2025 Role of malaria exposure and off-target responses on RTS,S/AS02A vaccine immunogenicity and protection in Mozambican children. NPJ vaccines 3 40473700
2025 Immunogenicity and efficacy in mice of two adjuvant formulations based on the C -and N-terminus of merozoite surface protein 1 of Plasmodium yoelii. Vaccine 2 40112557
2025 Full-length merozoite surface protein 1 formulated with GLA-SE adjuvant in malaria pre-exposed adults: a randomised, controlled, double-blind, parallel-group, single-centre Phase Ib trial. EClinicalMedicine 2 41210385
2025 Genetic polymorphism of Plasmodium falciparum using merozoite surface proteins 1 and 2 (msp-1 and msp-2) genes in Oveng and Mintom, South region of Cameroon. BMC infectious diseases 2 41257603
2026 Genetic polymorphisms of merozoite surface protein-1 ICB 5-6 in Vietnamese Plasmodium vivax isolates. Parasites, hosts and diseases 1 41549497
2025 IFN‑γ Production in Memory CD4 T Cells in Response to MSP119 Antigen and Its Correlation with Anemia and Thrombocytopenia in Pediatric Vivax Malaria. ACS omega 1 40584362
2025 Risk factor for gametocyte carriage and gametocytemia in Plasmodium vivax and Plasmodium falciparum. Infectious diseases of poverty 1 40759976
2025 A Comprehensive Analysis of Pfmsp1, Pfmsp2 and Pfcrt Genotypes in India and Global Perspectives for Evolving Epidemiological Patterns in Plasmodium falciparum. Indian journal of microbiology 1 42325444
2026 Iron-oxide nanoparticles (SPIONs) enhance malaria vaccine antibody response. Vaccine 0 41713326
2026 High genetic diversity, clonal activation of hypnozoites and relapse of Plasmodium vivax isolates in low-transmission setting of Ethiopia. Research square 0 41928784
2026 Hotspot-based integrated serosurveillance of neglected tropical diseases, malaria, and vaccine-preventable diseases in urban Guyana. Revista panamericana de salud publica = Pan American journal of public health 0 41982851
2026 Malaria antibody responses augment surveillance in low-transmission settings in the Upper River Region, the Gambia. Frontiers in epidemiology 0 42093919
2026 Genetic polymorphism and natural selection of merozoite surface protein 1 C-terminal 42 kDa in Vietnamese Plasmodium vivax isolates. Acta tropica 0 42176723
2026 Stage-aware transcriptomics reveals selective haplotype persistence in short-term ex vivo cultured Plasmodium vivax. bioRxiv : the preprint server for biology 0 42182277
2026 Comparative evaluation of four immunoassays for Plasmodium vivax serological detection using recombinant PvMSP1-42 antigen. PLoS neglected tropical diseases 0 42555573