Affinage · Plasmodium

HSP70

PF3D7_0818900 · heat shock protein 70

Annotated
2026-09-08
92 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_0818900 (HSP70/PfHsp70-1) is an abundant, soluble cytosolic and nuclear molecular chaperone of P. falciparum expressed across sporozoite, liver, and asexual erythrocytic stages and induced by heat shock, positioning it as a central proteostasis factor during febrile episodes (PMID:3095842, PMID:1779989, PMID:8153120). Its transcription is directly activated at elevated temperature by the transcription factor PfAP2-HS, which binds a tandem G-box motif in the hsp70-1 promoter; parasites lacking PfAP2-HS show reduced heat-shock survival (PMID:34400833). Biochemically, recombinant PfHsp70-1 is a largely monomeric ATPase with quantified basal activity, and its chaperone function depends on interdomain communication through the ATPase–substrate-binding-domain linker (residues V401/Q402), on an intact substrate-binding cavity, and on a C-terminal domain that thermally stabilizes the nucleotide-binding domain; the linker also governs self-association and client selection (PMID:14711509, PMID:15973516, PMID:19075824, PMID:19339102, PMID:38707424). Its ATPase-coupled folding cycle is stimulated by Hsp40/J-domain cochaperones — PfHsp40, Pfj1, Pfj4, and, promiscuously, isolated J-domains from multiple J-domain proteins — with which it cooperatively suppresses protein aggregation, and it associates nucleotide-dependently with the Hsp110 homolog PfHsp70-z acting as a nucleotide exchange factor (PMID:18674634, PMID:19339102, PMID:21191678, PMID:26894764, PMID:41618743). PfHsp70-1 assembles into a PfHsp90 multichaperone complex and forms a trimeric PfHsp70-1/PfHop/PfHsp90 assembly, with PfHop TPR1/TPR2B subdomains binding the PfHsp70-1 C-terminus in an ADP-favored manner (PMID:12584193, PMID:22005844, PMID:26267894). Functionally it folds client proteins including the ribonucleotide reductase small subunit PfR2 (delivered via the cochaperone PfYdj1's HPD motif), linking it to dNTP production and DNA replication, and it binds phosphatidylinositol 3-phosphate to stabilize the digestive vacuole under thermal stress (PMID:32975513, PMID:40938117). The protein is a validated antimalarial target, with multiple small molecules binding its nucleotide-binding or substrate-binding domains to inhibit ATPase/chaperone activity and parasite growth (PMID:28455613, PMID:29206141, PMID:40938117, PMID:42390429).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1986 Medium

    Establishing that P. falciparum encodes an abundant cytoplasmic Hsp70-family polypeptide defined the gene product as a candidate parasite chaperone.

    Evidence cDNA cloning, sequence analysis, and SDS-PAGE of parasite lysates

    PMID:3095842

    Open questions at the time
    • No biochemical chaperone or ATPase activity demonstrated yet
    • Subcellular localization not resolved
  2. 1991 Medium

    Demonstrating transient, temperature-dependent induction and nuclear localization tied the protein to the parasite heat-shock response.

    Evidence Northern blot, in vitro translation, and immuno-gold electron microscopy

    PMID:1779989

    Open questions at the time
    • Mechanism coupling induction to survival not shown
    • Cytosolic pool not addressed in this study
  3. 1994 Medium

    Showing expression across sporozoite, liver, and erythrocytic stages established the chaperone as constitutively required through the life cycle rather than a stage-restricted protein.

    Evidence Immunofluorescence, Western blot, and passive antibody transfer

    PMID:8153120

    Open questions at the time
    • Antibodies did not neutralize sporozoite infectivity, leaving a protective role unsupported
  4. 2003 Medium

    Co-sedimentation with PfHsp90 placed PfHsp70-1 within a defined multichaperone complex, moving it from a solo chaperone to a component of an assembled machine.

    Evidence Sedimentation analysis and size exclusion chromatography

    PMID:12584193

    Open questions at the time
    • No reciprocal pulldown
    • Bridging adaptor not identified at this stage
  5. 2004 High

    In vitro reconstitution quantified the intrinsic ATPase activity and monomeric state, establishing the enzymatic basis of the chaperone cycle; pharmacological disruption of the PfHsp90 complex linked it to ring-to-trophozoite progression.

    Evidence Heterologous expression with ATPase kinetics and gel filtration; geldanamycin complex disruption with flow cytometry

    PMID:14711509 PMID:15339915

    Open questions at the time
    • Cochaperone stimulation of ATPase not yet measured
    • Direct clients unknown
  6. 2009 High

    Domain dissection and mutagenesis defined how interdomain communication, the substrate-binding cavity, and the stabilizing C-terminal domain govern chaperone function.

    Evidence E. coli complementation with domain-swap chimeras and mutagenesis (2005), substrate-cavity mutagenesis with homology modeling (2008), and biophysical domain dissection (2009)

    PMID:15973516 PMID:19075824 PMID:19339102

    Open questions at the time
    • Structural model inferred by homology, not experimental structure
    • Client repertoire still undefined
  7. 2010 High

    Identifying Hsp40/J-domain cochaperones that stimulate ATPase activity and cooperate to suppress aggregation established the functional Hsp70–Hsp40 folding partnership in the parasite.

    Evidence Immunofluorescence co-localization, Hsp40-stimulated ATPase assays, and aggregation-suppression assays with Pfj1, Pfj4, and PfHsp40

    PMID:18674634 PMID:19339102 PMID:21191678

    Open questions at the time
    • Which J-proteins act on which clients in vivo not resolved
  8. 2015 High

    Defining the PfHop-bridged trimeric assembly and its domain/nucleotide dependence provided the molecular basis for coupling PfHsp70-1 to PfHsp90.

    Evidence Co-localization and co-IP/gel filtration (2011); far Western, SPR, and split-GFP mapping of TPR subdomain interactions (2015)

    PMID:22005844 PMID:26267894

    Open questions at the time
    • Client hand-off through the trimeric complex not directly demonstrated
  9. 2016 High

    Identifying PfHsp70-z as a nucleotide-dependent partner and candidate nucleotide exchange factor completed the core cochaperone cycle regulating PfHsp70-1.

    Evidence Co-immunoaffinity chromatography, SPR, and aggregation-suppression assays

    PMID:26894764

    Open questions at the time
    • NEF activity inferred, not kinetically demonstrated on PfHsp70-1
  10. 2020 High

    Discovery of PI(3)P binding and its requirement for digestive vacuole stability under heat shock revealed a non-canonical, lipid-linked role for the chaperone in thermal stress protection.

    Evidence Chemoproteomic PI(3)P pulldown, knockdown, inhibitor treatment, and live-cell microscopy

    PMID:32975513

    Open questions at the time
    • Structural basis of lipid binding unknown
    • Relationship between lipid binding and chaperone cycle unresolved
  11. 2021 High

    Mapping direct PfAP2-HS binding to a G-box motif in the hsp70-1 promoter identified the transcriptional switch driving heat-shock induction and drug tolerance.

    Evidence ChIP-seq, knockout parasites, and heat-shock/drug sensitivity assays

    PMID:34400833

    Open questions at the time
    • Whether HSP70 induction alone accounts for the survival phenotype not isolated
  12. 2025 High

    Defining the PfYdj1–PfHsp70-1 axis in folding ribonucleotide reductase subunit PfR2 connected the chaperone directly to dNTP production and DNA replication, and validated the cochaperone interface as a druggable node.

    Evidence Co-IP, HPD-motif mapping, small-molecule (116-9e) disruption, dNTP quantification, and synergy assays

    PMID:40938117

    Open questions at the time
    • Full client spectrum beyond PfR2 not defined
    • Linker-based client selection (2024) not yet integrated with in vivo client set
  13. 2026 Medium

    Domain-specific small molecules and promiscuous J-domain stimulation refined the mechanistic and druggability picture, while ESCRT linkage tied vesicular trafficking to PfHsp70-1-dependent proteostasis under heat stress.

    Evidence Thermal shift/MST/competition assays for AMK3/AMK4 domain binding; in vitro J-domain ATPase stimulation; PfVps60 knockout with proteomics and heat-shock viability

    PMID:41618743 PMID:42253101 PMID:42390429

    Open questions at the time
    • ESCRT effect on HSP70 induction is downstream/indirect
    • Physiological hierarchy among promiscuous J-domain partners unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full in vivo client repertoire of PfHsp70-1 and an experimental high-resolution structure of the parasite chaperone in its cochaperone-bound states remain undefined.
  • No experimental atomic structure captured in the corpus
  • Comprehensive in-cell client and interactome map incomplete
  • Genetic essentiality tested largely by knockdown/pharmacology rather than clean knockout

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
EXPORTED P. FALCIPARUM J-DOMAIN PROTEINS (ISOLATED J-DOMAINS) [#30]PFHOP (HSP70-HSP90 ORGANIZING PROTEIN) [#18, #20]PFHSP40 [#17]PFHSP70-Z (HSP110 HOMOLOG, NUCLEOTIDE EXCHANGE FACTOR) [#21, #26]PFHSP90 [#7, #18, #20]PFJ1 (DNAJ HOMOLOG, PFD0465W) [#15]PFJ4 (TYPE II HSP40) [#14]PFR2 (RIBONUCLEOTIDE REDUCTASE SMALL SUBUNIT, CLIENT) [#27]PFYDJ1 (PF3D7_1437900, CYTOSOLIC TYPE I HSP40) [#27]
Complex memberships
PfHsp70-1/PfHop/PfHsp90 trimeric complex [#18, #20]PfHsp90 multichaperone complex (~300 kDa / ~11S, containing PfHsp70-1, PfPP5, tubulin) [#7, #9]

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 PF3D7_0818900 (HSP70/PfHsp70-1) encodes an abundant, soluble cytoplasmic polypeptide of ~75 kDa present in all asexual blood stages and gametocytes, containing tandemly repeated Gly-Gly-Met-Pro sequences, and is 70% homologous at the amino acid level to Drosophila hsp70. cDNA cloning, nucleotide sequence analysis, SDS-PAGE of parasite lysates Proceedings of the National Academy of Sciences of the United States of America Medium 3095842
1991 HSP70 (PfHsp70-1/Pfhsp) is induced by heat shock (temperature elevation from 26°C to 37°C and higher) in a transient, temperature-dependent manner; mRNA levels increase in parallel with protein synthesis. Immuno-gold electron microscopy localized Pfhsp to the nucleus of the parasite. Northern blot, in vitro translation, immuno-gold electron microscopy, metabolic labeling Molecular and biochemical parasitology Medium 1779989
1992 Expression of HSP70 (PfHsp70-1/PFHSP70-I) gene is enhanced after heat shock, and parasites remain viable after heat shock but show altered growth, suggesting HSP70 overexpression contributes to parasite survival during fever. Parasite viability assay, growth assay, heat-shock protein expression analysis FEBS letters Low 1385215
1994 HSP70 (PfHsp70-1) protein is expressed in sporozoites, liver stages, and erythrocytic forms of malaria parasites, as demonstrated by monoclonal antibodies reacting with a recombinant protein encoding the carboxyl terminal half (aa 365–681). Passive transfer of these antibodies failed to neutralize sporozoite infectivity. Immunofluorescence, Western blot, passive transfer experiments with monoclonal antibodies Parasitology research Medium 8153120
1998 HSP70 (HSC70 ortholog) from Plasmodium knowlesi merozoites binds F-actin and forms a complex with 32/34-kDa proteins; this HSC70/32/34-kDa complex inhibits actin polymerization in vitro in a calcium-independent manner abrogated by phosphatidylinositol 4,5-bisphosphate, consistent with a barbed-end capping activity. F-actin affinity chromatography, ATP-agarose binding, tryptic peptide microsequencing, Western blot, gel filtration chromatography, in vitro actin polymerization assay Molecular and biochemical parasitology Medium 9662713
2001 In P. falciparum-infected erythrocytes, host-cell Hsp70 (human, not parasite-encoded) is recruited into membrane-bound, detergent-resistant complexes in an ATP-dependent manner, and can be cross-linked to the knob subunit PfHRP1 at the erythrocyte surface, implicating host Hsp70 in knob assembly. No parasite-encoded HSP70 was detected in the erythrocyte cytoplasm at this time. Hypotonic lysis, detergent solubilization, sedimentation analysis, chemical cross-linking, co-immunoprecipitation The Journal of biological chemistry Medium 11711553
2003 Putative HSP70 (DnaK) binding sites present in apicoplast transit peptides are important for correct apicoplast targeting in vivo; site-directed mutagenesis of these sites disrupted organellar targeting. Site-directed mutagenesis, in vivo organellar targeting assay Science (New York, N.Y.) Medium 12560551
2003 PfHsp70 (HSP70/PF3D7_0818900) co-sediments with PfHsp90 in ~300 kDa, ~11S complexes, demonstrating it is a component of the PfHsp90 multi-chaperone complex in the parasite. Sedimentation analysis, size exclusion chromatography The Journal of biological chemistry Medium 12584193
2004 Recombinant PfHsp70-1 (HSP70/PF3D7_0818900) was overproduced in E. coli and biochemically characterized: it exhibits basal ATPase activity with Vmax = 14.6 nmol/min/mg, Km = 616.5 µM, kcat = 1.03 min⁻¹, and exists largely as a monomer in solution. Heterologous overexpression in E. coli, nickel-chelating affinity chromatography, ATPase activity assay, gel filtration Protein expression and purification High 14711509
2004 Geldanamycin disrupts the PfHsp90 multi-chaperone complex that contains PfHsp70 (HSP70/PF3D7_0818900), PfPP5, and tubulin, and inhibits parasite progression from ring to trophozoite stage; repeated heat exposure (mimicking fever) promotes parasite development through this complex. Geldanamycin treatment, flow cytometry, complex disruption assay The Journal of biological chemistry Medium 15339915
2005 PfHsp70-1 (HSP70/PF3D7_0818900) functionally complements an E. coli dnaK756 mutant (thermosensitive) but not the dnaK deletion or truncation mutant. Two key amino acid residues (V401 and Q402) in the linker region between the ATPase domain and substrate-binding domain are essential for in vivo chaperone function. The substrate-binding domain of PfHsp70, when fused to the E. coli DnaK ATPase domain, retained complementation activity, demonstrating that interdomain communication is critical. In vivo complementation assay in E. coli, domain-swap chimera construction, site-directed mutagenesis Molecular genetics and genomics : MGG High 15973516
2006 15-deoxyspergualin (DSG) binds PfHsp70-1 (HSP70/PF3D7_0818900, which carries a C-terminal EEVD motif) and further stimulates its ATP-enhanced chaperone activity, but has no effect on PfHsp70-2 (which lacks EEVD). Substrate binding to PfHsp70-1 is unaffected by DSG, suggesting DSG acts via the EEVD motif to modulate ATPase-coupled chaperone cycling. Cloning, overexpression, chaperone activity assay, binding assay in presence/absence of DSG and ATP Biochemical and biophysical research communications Medium 16884692
2006 15-deoxyspergualin causes Hsp70 (HSP70/PF3D7_0818900) sequestration, leading to phosphorylation of eIF2α and stalling of protein synthesis in P. falciparum, though this requires high micromolar concentrations. At lower concentrations, DSG primarily targets trafficking of nucleus-encoded proteins to the apicoplast. Metabolic labeling, eIF2α phosphorylation assay, protein trafficking assay The Journal of biological chemistry Medium 17194705
2008 PfHsp70-1 (HSP70/PF3D7_0818900) displays chaperone activity in vitro; amino acid substitutions introduced in the substrate-binding cavity compromise its chaperone function. Three-dimensional homology modeling was used to map domain spatial orientation. 3D homology modeling, site-directed mutagenesis, in vitro chaperone activity assay Protein and peptide letters Medium 19075824
2008 PfHsp70-1 (HSP70/PF3D7_0818900) and Pfj4 (a type II Hsp40) co-localize to the nucleus and cytoplasm of the parasite, and immunoprecipitation studies and size exclusion chromatography indicate that they directly or indirectly interact. Immunofluorescence, immuno-electron microscopy, immunoprecipitation, size exclusion chromatography, Western blot The international journal of biochemistry & cell biology Medium 18674634
2009 PfHsp70-1 (HSP70/PF3D7_0818900) has chaperone activity that is enhanced by Pfj1 (PFD0465w, the DnaJ homolog), representing the first evidence for a functional Pfj1–PfHsp70-1 interaction. The C-terminal domain of PfHsp70-1 confers thermal stability to the N-terminal nucleotide-binding domain and functions as a stabilization domain. Fluorescence spectroscopy, circular dichroism, in vitro chaperone activity assay, domain deletion analysis Biophysical chemistry High 19339102
2009 Pyrimidinone-amide compounds alter the ATPase activity of purified PfHsp70-1 (HSP70/PF3D7_0818900) in single-turnover assays and inhibit P. falciparum replication, demonstrating that PfHsp70-1 ATPase activity can be pharmacologically modulated. Single-turnover ATPase assay with purified recombinant PfHsp70, parasite growth inhibition assay Bioorganic & medicinal chemistry Medium 19195901
2010 PfHsp70-1 (HSP70/PF3D7_0818900) and PfHsp40 co-localize mainly in the parasite cytosol; recombinant PfHsp40 stimulates the ATPase activity of PfHsp70-1 similarly to canonical Hsp40s. PfHsp40 cooperates with PfHsp70-1 to suppress protein aggregation in vitro. Pyrimidinone-based small molecules differentially inhibit the Hsp40-stimulated ATPase activities of plasmodial versus human Hsp70. Indirect immunofluorescence microscopy, ATPase activity assay (Hsp40-stimulated), protein aggregation suppression assay, pharmacological inhibition Cell stress & chaperones High 21191678
2011 PfHop (PfHsp70-Hsp90 organising protein) co-localizes with PfHsp70-1 (HSP70/PF3D7_0818900) and PfHsp90 at the trophozoite stage, and co-immunoprecipitation and gel filtration confirm they form a trimeric complex, suggesting PfHop mediates functional interaction between PfHsp70-1 and PfHsp90. Co-immunoprecipitation, gel filtration chromatography, immunofluorescence co-localization Cell stress & chaperones Medium 22005844
2011 Purified recombinant PfHsp70-1 (HSP70/PF3D7_0818900) chaperone activity (protein aggregation suppression) is inhibited in a concentration-dependent manner by malonganenones A–C, lapachol and bromo-β-lapachona; most of these compounds also inhibit parasite growth. Malate dehydrogenase-based aggregation suppression assay, parasite growth inhibition assay Biological chemistry Medium 21426241
2015 PfHop interacts directly with PfHsp70-1 (HSP70/PF3D7_0818900) in a nucleotide-dependent fashion; ADP promotes the association more than ATP. The TPR1 and TPR2B subdomains of PfHop preferentially bind the C-terminus of PfHsp70-1, while TPR2A preferentially binds PfHsp90 C-terminus, defining the molecular basis for assembly of the PfHsp70-1/PfHop/PfHsp90 complex. Far Western blot, surface plasmon resonance (SPR), co-immunoprecipitation, split-GFP domain interaction assay PloS one High 26267894
2016 PfHsp70-z (an Hsp110 homolog) associates with PfHsp70-1 (HSP70/PF3D7_0818900) in a nucleotide-dependent fashion as shown by co-immunoaffinity chromatography and surface plasmon resonance. PfHsp70-z possesses independent chaperone activity (protein aggregation suppression) marginally greater than PfHsp70-1, and may serve as a nucleotide exchange factor (NEF) for PfHsp70-1. Co-immunoaffinity chromatography, surface plasmon resonance, protein aggregation suppression assay Cell stress & chaperones High 26894764
2017 Polymyxin B (PMB) directly binds PfHsp70-1 (HSP70/PF3D7_0818900) as shown by SPR, and modulates its secondary and tertiary structure (circular dichroism, tryptophan fluorescence), inhibiting both its basal ATPase activity and chaperone function. Surface plasmon resonance, circular dichroism spectroscopy, tryptophan fluorescence, ATPase assay, chaperone aggregation suppression assay Cell stress & chaperones High 28455613
2017 (-)-Epigallocatechin-3-gallate (EGCG) directly binds PfHsp70-1 (HSP70/PF3D7_0818900) as shown by SPR, induces secondary and tertiary conformational changes, inhibits ATPase and chaperone functions, abrogates its association with functional partners, and inhibits parasite growth (IC50 ~2.9 µM). Surface plasmon resonance, circular dichroism, ATPase assay, aggregation suppression assay, parasite growth assay Molecules (Basel, Switzerland) High 29206141
2020 A chemoproteomic approach identified PfHsp70-1 (HSP70/PF3D7_0818900) as a phosphatidylinositol 3-phosphate (PI(3)P)-binding protein. Hsp70 inhibitor treatment and knockdown of PfHsp70-1 phenocopy PI(3)P-deficient parasites under heat shock (destabilization of the digestive vacuole). PfHsp70-1 knockdown hypersensitizes parasites to heat shock and PI3K inhibitors, establishing a mechanistic link between PI(3)P and PfHsp70-1 in digestive vacuole stabilization during thermal stress. Chemoproteomic pulldown (PI(3)P-binding identification), Hsp70 inhibitor treatment, PfHsp70-1 knockdown, live cell microscopy, pharmacological rescue experiments eLife High 32975513
2021 The transcription factor PfAP2-HS activates transcription of hsp70-1 (PF3D7_0818900) and hsp90 at elevated temperatures. The primary PfAP2-HS binding site in the genome coincides with a tandem G-box DNA motif in the hsp70-1 promoter. Parasites lacking PfAP2-HS have reduced heat-shock survival and increased sensitivity to artemisinin and proteasome inhibitor epoxomicin. ChIP-seq (PfAP2-HS binding site mapping), engineered knockout parasites, heat-shock survival assay, drug sensitivity assay Nature microbiology High 34400833
2024 The linker region of PfHsp70-1 (HSP70/PF3D7_0818900) is important for its self-association and client selection. Swapping the linker with that of PfHsp70-z (an Hsp110 homolog) compromises both self-association (measured by SPR) and client binding specificity (measured by co-affinity chromatography coupled to LC-MS). Surface plasmon resonance, co-affinity chromatography, LC-MS Heliyon Medium 38707424
2025 PfHsp70-1 (HSP70/PF3D7_0818900) serves as the chaperone partner for the cochaperone PfYdj1 (PF3D7_1437900/cytosolic type I Hsp40) in folding ribonucleotide reductase small subunit (PfR2). PfR2 interacts specifically with PfYdj1, which then interacts with PfHsp70-1 via its HPD motif. Small molecule 116-9e disrupts the PfYdj1–PfHsp70-1 interaction, destabilizes PfR2, inhibits dNTP production, and causes replication arrest in parasites. Combination of 116-9e with a PfR2 catalytic inhibitor (benzo-hydroxamate) acts synergistically. Co-immunoprecipitation, small molecule perturbation (116-9e), dNTP quantification, parasite growth and replication assay, synergy assay mBio High 40938117
2026 In P. falciparum, loss of ESCRT protein PfVps60 reduces induction of cytosolic PfHsp70-1 (HSP70/PF3D7_0818900) upon heat shock, alters aggregation dynamics, and results in early loss of parasite viability following heat shock, linking vesicular trafficking to PfHsp70-1-mediated proteostasis during thermal stress. PfVps60 knockout, proteomic profiling of EV cargo, heat-shock viability assay, protein aggregation analysis Emerging microbes & infections Medium 42253101
2026 Small molecule inhibitors AMK3 and AMK4 bind PfHsp70-1 (HSP70/PF3D7_0818900) with low-micromolar affinity and >25-fold selectivity over human HSPA1A. AMK3 binds the N-terminal nucleotide-binding domain and competes with ATP binding; AMK4 binds the C-terminal substrate-binding domain and disrupts peptide binding. Both exhibit anti-Plasmodium activity. High-throughput thermal shift screen, microscale thermophoresis, proteomics-based binding region mapping, biochemical competition assay, parasite growth assay Antimicrobial agents and chemotherapy High 42390429
2026 Isolated J-domains from multiple exported P. falciparum J-domain proteins stimulate the ATPase activity of PfHsp70-1 (HSP70/PF3D7_0818900) in vitro, demonstrating promiscuous stimulation. Differences in stimulation efficiency were observed between individual PfJDP–PfHsp70-1 pairings. In vitro ATPase stimulation assay with purified isolated J-domains and recombinant PfHsp70-1 FEBS open bio Medium 41618743

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum. Science (New York, N.Y.) 370 12560551
2003 Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes. The Journal of biological chemistry 190 12584193
1994 Demonstration of heat-shock protein 70 in the sporozoite stage of malaria parasites. Parasitology research 182 8153120
1986 A repetitive antigen of Plasmodium falciparum that is homologous to heat shock protein 70 of Drosophila melanogaster. Proceedings of the National Academy of Sciences of the United States of America 159 3095842
1991 Induction and localization of Plasmodium falciparum stress proteins related to the heat shock protein 70 family. Molecular and biochemical parasitology 144 1779989
2012 Plasmodium falciparum-encoded exported hsp70/hsp40 chaperone/co-chaperone complexes within the host erythrocyte. Cellular microbiology 119 22925632
2007 Chaperoning a cellular upheaval in malaria: heat shock proteins in Plasmodium falciparum. Molecular and biochemical parasitology 111 17307260
2007 The Hsp40 proteins of Plasmodium falciparum and other apicomplexa: regulating chaperone power in the parasite and the host. The international journal of biochemistry & cell biology 111 17428722
2007 The structural and functional diversity of Hsp70 proteins from Plasmodium falciparum. Protein science : a publication of the Protein Society 103 17766381
1990 A malaria heat-shock-like determinant expressed on the infected hepatocyte surface is the target of antibody-dependent cell-mediated cytotoxic mechanisms by nonparenchymal liver cells. European journal of immunology 102 2201546
2007 Systems analysis of chaperone networks in the malarial parasite Plasmodium falciparum. PLoS computational biology 94 17941702
2011 Intracellular protozoan parasites of humans: the role of molecular chaperones in development and pathogenesis. Protein and peptide letters 90 20955165
2009 Plasmodial heat shock proteins: targets for chemotherapy. FEMS immunology and medical microbiology 88 20041948
2012 Plasmodium falciparum-infected erythrocytes induce granzyme B by NK cells through expression of host-Hsp70. PloS one 81 22438997
2001 Host chaperones are recruited in membrane-bound complexes by Plasmodium falciparum. The Journal of biological chemistry 80 11711553
1988 Plasmodium falciparum gene encoding a protein similar to the 78-kDa rat glucose-regulated stress protein. Proceedings of the National Academy of Sciences of the United States of America 80 3045815
2004 Recurrent fever promotes Plasmodium falciparum development in human erythrocytes. The Journal of biological chemistry 71 15339915
1987 The primary structure of a Plasmodium falciparum polypeptide related to heat shock proteins. Molecular and biochemical parasitology 68 2448622
2009 Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum. Bioorganic & medicinal chemistry 67 19195901
2009 Characterisation of Plasmodium invasive organelles; an ookinete microneme proteome. Proteomics 64 19206106
2004 Overproduction, purification, and characterization of the Plasmodium falciparum heat shock protein 70. Protein expression and purification 61 14711509
2013 KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro. Antimicrobial agents and chemotherapy 60 24366744
2011 Characterisation of the Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop). Cell stress & chaperones 59 22005844
1992 Antibodies and reactive T cells against the malaria heat-shock protein Pf72/Hsp70-1 and derived peptides in individuals continuously exposed to Plasmodium falciparum. Journal of immunology (Baltimore, Md. : 1950) 56 1431109
2019 The Plasmodium falciparum Hsp70-x chaperone assists the heat stress response of the malaria parasite. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 52 31690116
2001 Cellular stress and injury responses in the brains of adult Vietnamese patients with fatal Plasmodium falciparum malaria. Neuropathology and applied neurobiology 52 11903925
2006 15-Deoxyspergualin modulates Plasmodium falciparum heat shock protein function. Biochemical and biophysical research communications 51 16884692
2005 Plasmodium falciparum heat shock protein 70 is able to suppress the thermosensitivity of an Escherichia coli DnaK mutant strain. Molecular genetics and genomics : MGG 51 15973516
2017 The exported chaperone Hsp70-x supports virulence functions for Plasmodium falciparum blood stage parasites. PloS one 49 28732045
2014 Selective modulation of plasmodial Hsp70s by small molecules with antimalarial activity. Biological chemistry 49 24854538
2010 Plasmodium falciparum encodes a single cytosolic type I Hsp40 that functionally interacts with Hsp70 and is upregulated by heat shock. Cell stress & chaperones 49 21191678
2021 A heat-shock response regulated by the PfAP2-HS transcription factor protects human malaria parasites from febrile temperatures. Nature microbiology 48 34400833
2011 Screening for small molecule modulators of Hsp70 chaperone activity using protein aggregation suppression assays: inhibition of the plasmodial chaperone PfHsp70-1. Biological chemistry 48 21426241
2008 Structure-function study of a Plasmodium falciparum Hsp70 using three dimensional modelling and in vitro analyses. Protein and peptide letters 47 19075824
2016 Plasmodium falciparum Hsp70-z, an Hsp110 homologue, exhibits independent chaperone activity and interacts with Hsp70-1 in a nucleotide-dependent fashion. Cell stress & chaperones 46 26894764
2017 The Exported Chaperone PfHsp70x Is Dispensable for the Plasmodium falciparum Intraerythrocytic Life Cycle. mSphere 45 28959740
2011 Gold nanoparticle-based fluorescence immunoassay for malaria antigen detection. Analytical and bioanalytical chemistry 44 22089818
2010 Malaria heat shock proteins: drug targets that chaperone other drug targets. Infectious disorders drug targets 44 20334623
2008 The Plasmodium falciparum heat shock protein 40, Pfj4, associates with heat shock protein 70 and shows similar heat induction and localisation patterns. The international journal of biochemistry & cell biology 43 18674634
2005 Enhancement of DNA vaccine potency by linkage of Plasmodium falciparum malarial antigen gene fused with a fragment of HSP70 gene. Vaccine 43 15629354
2016 Rapid Generation of Marker-Free P. falciparum Fluorescent Reporter Lines Using Modified CRISPR/Cas9 Constructs and Selection Protocol. PloS one 42 27997583
1988 A second antigenic heat shock protein of Plasmodium falciparum. DNA (Mary Ann Liebert, Inc.) 42 3282854
2019 Dual RNA-seq identifies human mucosal immunity protein Mucin-13 as a hallmark of Plasmodium exoerythrocytic infection. Nature communications 41 30700707
2015 Plasmodium falciparum Hop (PfHop) Interacts with the Hsp70 Chaperone in a Nucleotide-Dependent Fashion and Exhibits Ligand Selectivity. PloS one 40 26267894
2017 Polymyxin B inhibits the chaperone activity of Plasmodium falciparum Hsp70. Cell stress & chaperones 39 28455613
2015 Overexpression, Purification and Characterisation of the Plasmodium falciparum Hsp70-z (PfHsp70-z) Protein. PloS one 39 26083397
2018 Structural and biochemical characterization of Plasmodium falciparum Hsp70-x reveals functional versatility of its C-terminal EEVN motif. Proteins 38 30183110
2006 15-deoxyspergualin primarily targets the trafficking of apicoplast proteins in Plasmodium falciparum. The Journal of biological chemistry 38 17194705
2019 Cholesterol bound Plasmodium falciparum co-chaperone 'PFA0660w' complexes with major virulence factor 'PfEMP1' via chaperone 'PfHsp70-x'. Scientific reports 37 30804381
2017 (-)-Epigallocatechin-3-Gallate Inhibits the Chaperone Activity of Plasmodium falciparum Hsp70 Chaperones and Abrogates Their Association with Functional Partners. Molecules (Basel, Switzerland) 35 29206141
2021 Design and synthesis of quinoline-pyrimidine inspired hybrids as potential plasmodial inhibitors. European journal of medicinal chemistry 34 33744688
2015 Plasmodial HSP70s are functionally adapted to the malaria parasite life cycle. Frontiers in molecular biosciences 34 26167469
2016 J-dot targeting of an exported HSP40 in Plasmodium falciparum-infected erythrocytes. International journal for parasitology 33 27063072
2009 Hsp70-1 from Plasmodium falciparum: protein stability, domain analysis and chaperone activity. Biophysical chemistry 33 19339102
1998 Actin-binding proteins of invasive malaria parasites and the regulation of actin polymerization by a complex of 32/34-kDa proteins associated with heat shock protein 70kDa. Molecular and biochemical parasitology 33 9662713
1990 Glycolipid anchorage of Plasmodium falciparum surface antigens. Research in immunology 33 1708512
2020 Phosphatidylinositol 3-phosphate and Hsp70 protect Plasmodium falciparum from heat-induced cell death. eLife 32 32975513
2013 Hsp70s and J proteins of Plasmodium parasites infecting rodents and primates: structure, function, clinical relevance, and drug targets. Current pharmaceutical design 32 22920898
2016 The Malarial Exported PFA0660w Is an Hsp40 Co-Chaperone of PfHsp70-x. PloS one 31 26845441
2019 Comparative structure-function features of Hsp70s of Plasmodium falciparum and human origins. Biophysical reviews 30 31280465
2013 Identification of an exported heat shock protein 70 in Plasmodium falciparum. Parasite (Paris, France) 30 23340228
2007 Detection of malaria infection via latex agglutination assay. Analytical chemistry 30 17511424
2014 Plasmodial Hsp40 and Hsp70 chaperones: current and future perspectives. Parasitology 29 24666996
2021 General Structural and Functional Features of Molecular Chaperones. Advances in experimental medicine and biology 27 34569020
2015 Oxidative stress-mediated antimalarial activity of plakortin, a natural endoperoxide from the tropical sponge Plakortis simplex. Free radical biology & medicine 27 26459031
2013 Malaria proteomics: insights into the parasite-host interactions in the pathogenic space. Journal of proteomics 27 24140976
1992 Effect of heat-shock on Plasmodium falciparum viability, growth and expression of the heat-shock protein 'PFHSP70-I' gene. FEBS letters 27 1385215
2017 Identification of O-GlcNAcylated proteins in Plasmodium falciparum. Malaria journal 25 29187233
2016 Trafficking of the exported P. falciparum chaperone PfHsp70x. Scientific reports 25 27824087
2013 Plasmodium falciparum Hsp70-x: a heat shock protein at the host-parasite interface. Journal of biomolecular structure & dynamics 24 24028577
2017 Plasmodium Hsp40 and human Hsp70: A potential cochaperone-chaperone complex. Molecular and biochemical parasitology 23 28322872
2006 Microbial heat shock protein 70 stimulatory properties have different TLR requirements. Vaccine 22 17049413
2025 Two sides of the same coin: heat shock proteins as biomarkers and therapeutic targets for some complex diseases. Frontiers in molecular biosciences 10 40051500
2024 Plasmodium falciparum heat shock proteins as antimalarial drug targets: An update. Cell stress & chaperones 7 38518861
2024 A promising class of antiprotozoal agents, design and synthesis of novel Pyrimidine-Cinnamoyl hybrids. European journal of medicinal chemistry 5 39549508
2024 Phytochemical evaluation of Ziziphus mucronata and Xysmalobium undulutum towards the discovery and development of anti-malarial drugs. Malaria journal 4 38734650
2025 Development of a multi-epitope vaccine candidate targeting blood-stage of malaria through immunoinformatics approach. Human immunology 3 40669099
2024 Swapping the linkers of canonical Hsp70 and Hsp110 chaperones compromises both self-association and client selection. Heliyon 3 38707424
2024 The J Domain Proteins of Plasmodium knowlesi, a Zoonotic Malaria Parasite of Humans. International journal of molecular sciences 3 39596368
2025 Inhibition of the assembly of Plasmodium Hsp70-1 and Hsp40 complex blocks DNA replication by destabilizing ribonucleotide reductase subunit-2. mBio 2 40938117
2026 Promiscuous stimulation of HSP70 ATPase activity by parasite-derived J-domains. FEBS open bio 1 41618743
2025 Computational Prioritization of T Cell Epitopes to Overcome HLA Restriction and Antigenic Diversity in Plasmodium falciparum. bioRxiv : the preprint server for biology 1 40791414
2026 Flow cytometry-based evaluation of hepatic infection by non-fluorescent Plasmodium parasites. International journal for parasitology 0 41864451
2026 Is the Association of Granzyme B and the Exported Parasite Hsp70 a Possible Trojan Horse of Severe Malaria? Advances in experimental medicine and biology 0 42213323
2026 Extracellular vesicles participate in proteostasis and heat shock adaptation in Plasmodium falciparum. Emerging microbes & infections 0 42253101
2026 Plasmodium falciparum leucine-rich repeat 5 disruption alters the transcription progression during asexual and sexual stage development. mSphere 0 42294623
2026 Proteogenomic Analysis of CDPK1 Mutant in Plasmodium falciparum. Omics : a journal of integrative biology 0 42300840
2026 Development of domain-specific probes of Plasmodium falciparum heat shock protein 70-1. Antimicrobial agents and chemotherapy 0 42390429
2026 Isolation and Characterisation of Phage-Displayed scFv Antibodies Targeting PfHSP70 and PfLDH of Plasmodium falciparum. Biochemistry research international 0 42502673
2025 Expanding the fluorescent toolkit: Blue fluorescent protein-expressing Plasmodium berghei for enhanced multiplex microscopy. PloS one 0 40029851
2025 Biochemical and biophysical characterization of Plasmodium falciparum glucose regulated protein 170. Scientific reports 0 40730633
2025 Acanthospermum australe Extract Inhibits the Chaperone Activity of Plasmodium falciparum Heat Shock Protein 70-1. Microorganisms 0 41011525