Affinage · Plasmodium

MyoA

PF3D7_1342600 · myosin A

Annotated
2026-09-08
58 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PfMyoA (PF3D7_1342600) is a class XIV unconventional single-headed myosin motor that powers the actin-based gliding machinery underlying Plasmodium erythrocyte invasion and life-cycle motility (PMID:9625746, PMID:31337750). The protein is synthesized in mature schizonts and merozoites and anchored to the parasite periphery beneath the plasma membrane adjacent to the inner membrane complex, a localization determined by its short 15-residue C-terminal tail — including two essential arginines — that mediates membrane attachment independently of the F-actin cytoskeleton (PMID:9625746, PMID:10749937). This same tail helix binds the light chain MTIP (Kd ~235 nM), and reconstitution of the MTIP–PfMyoA complex drives actin filament movement at ~3.5 µm/s, comparable to fast muscle myosins (PMID:16337961). A second light chain, PfELC, binds an adjacent degenerate IQ motif contingent on prior MTIP binding, and together the two light chains act as a lever arm that enhances motor velocity to match skeletal-muscle-actin gliding speeds (PMID:28978649, PMID:33046215). Crystallographic and cryo-EM work has resolved the MTIP–tail interface, the compact clamp conformation, the full-length motor in distinct catalytic states, and the conserved actomyosin footprint on PfAct1 (PMID:16547135, PMID:17628590, PMID:33046215, PMID:33767187). Motor output is tuned by phosphorylation of heavy-chain Ser19 — the unphosphorylated form favors ensemble force generation at reduced speed while phosphorylation increases speed — and by phosphorylation of MTIP Ser107/Ser108, which loosens the MTIP grip on the tail; upstream, PfPKG, CDPK1, and PKA converge on the motor complex (PMID:18768477, PMID:22932904, PMID:23025827, PMID:26149123, PMID:31337750). Genetic ablation and phospho-mutant studies establish that active PfMyoA is essential for gliding, ookinete motility and mosquito transmission, and defines distinct mechanical barriers to RBC invasion, and the ATPase inhibitor KNX-002 blocks blood-stage growth by trapping the motor detached from actin (PMID:21899701, PMID:33104759, PMID:35506479, PMID:37308472).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1998 Medium

    Establishing when and where PfMyoA acts required defining its stage expression and subcellular position; this study showed it is a merozoite/schizont peripheral protein tightly associated with the membrane at the IMC.

    Evidence Immunoblot staging, subcellular fractionation, IFA and immuno-gold EM in P. falciparum

    PMID:9625746

    Open questions at the time
    • Did not identify the molecular anchor mediating membrane association
    • No direct functional readout of motor activity
  2. 2000 Medium

    The determinant of PfMyoA's membrane localization was unknown; mutagenesis identified the 15-residue C-terminal tail and two essential arginines as necessary and sufficient for peripheral targeting.

    Evidence Truncation, site-directed mutagenesis and GFP fusions (tail motif characterized for PfM-A; primary constructs in Toxoplasma)

    PMID:10749937

    Open questions at the time
    • Binding partner engaged by the tail not identified here
    • Core experimental work performed in the Toxoplasma ortholog
  3. 2003 Medium

    What the PfMyoA tail binds was unresolved; a yeast two-hybrid screen identified MTIP as the specific tail-interacting partner at the IMC, linking the motor to the membrane skeleton.

    Evidence Yeast two-hybrid with deletion analysis and sporozoite co-localization

    PMID:12456714

    Open questions at the time
    • Binding affinity and stoichiometry not quantified
    • Motor activity of the complex not tested
  4. 2005 High

    Whether the MTIP–PfMyoA complex is a functional motor was untested; quantitative binding and in vitro motility assays showed a stable complex (Kd ~235 nM) that drives fast actin gliding at 3.5 µm/s.

    Evidence Co-IP, surface plasmon resonance, in vitro actin gliding, peptide competition in P. falciparum

    PMID:16337961

    Open questions at the time
    • Second light chain not yet identified
    • Regulation of motor speed not addressed
  5. 2006 High

    The broader motor assembly and the atomic basis of tail recognition were undefined; co-IP placed PfMyoA in a stable glideosome with MTIP/GAP45/GAP50 and crystallography revealed MTIP undergoes large conformational changes to grip the tail helix.

    Evidence Co-IP/IFA of glideosome components and X-ray crystallography with growth-inhibition assay in P. falciparum

    PMID:16321976 PMID:16513191 PMID:16547135

    Open questions at the time
    • Whether membrane anchoring is via GAP proteins not resolved
    • Functional consequence of each GAP subunit for motor output untested
  6. 2007 High

    The conformational details of the clamped complex were unknown; crystallography plus mutagenesis showed both MTIP domains fully surround the tail at neutral pH, with residues H810 and K813 essential for the compact complex.

    Evidence X-ray crystallography and site-directed mutagenesis in P. falciparum

    PMID:17628590

    Open questions at the time
    • How the clamp is released or regulated not addressed
    • In-parasite consequence of clamp mutations not tested
  7. 2008 High

    How the motor complex is regulated was unclear; CDPK1 was shown to phosphorylate MTIP (Ser47) and GAP45, localize to the merozoite periphery, and its inhibition blocked invasion, implicating kinase control of the motor.

    Evidence In vitro kinase assay with MS phosphosite mapping, IFA and chemical inhibition in P. falciparum

    PMID:18768477

    Open questions at the time
    • Direct effect of MTIP Ser47 phosphorylation on motor activity not measured
    • Whether PfMyoA heavy chain is a CDPK1 substrate not established here
  8. 2009 Medium

    Whether PfMyoA function extends beyond invasion was unknown; a MyoA tail-only dominant negative phenocopied Rab11A loss, revealing a requirement for the motor in IMC assembly and cytokinesis.

    Evidence Rab11A–MTIP co-IP, inducible dominant-negative expression, IFA in P. falciparum

    PMID:19165333

    Open questions at the time
    • Dominant-negative may titrate MTIP rather than reflect endogenous motor role
    • Mechanism linking motor to IMC maturation not defined
  9. 2010 Medium

    The solution behavior of the interface and additional head-domain partners were undefined; NMR showed MTIP is dynamic and unstable without the tail, and a separate study mapped PfDLC1 binding to head-domain motifs.

    Evidence Solution NMR of the complex; domain-mapping/co-IP and co-localization for PfDLC1 in P. falciparum

    PMID:20174678 PMID:20421304

    Open questions at the time
    • Functional consequence of the PfDLC1–PfMyoA interaction unresolved
    • NMR study lacked mutagenesis validation
  10. 2011 High

    Whether MyoA is genetically essential for motility in vivo was untested; stage-specific depletion of PbMyoA abolished ookinete gliding and blocked mosquito transmission.

    Evidence Promoter-swap conditional knockdown with gliding and transmission assays in P. berghei

    PMID:21899701

    Open questions at the time
    • Molecular basis of motility loss not dissected
    • Does not address asexual blood-stage essentiality
  11. 2012 High

    The mechanistic role of interface phosphorylation was unknown; structural and biophysical work showed phosphomimetic MTIP Ser108/Ser107 breaks the tight clamp around the tail, and PKA was identified as an additional kinase acting on PfMyoA and GAP45.

    Evidence Crystallography, NMR relaxation, biophysical binding, parasite-lysate pull-downs; phosphoproteomics with in vitro kinase assay in P. falciparum

    PMID:22932904 PMID:23025827

    Open questions at the time
    • In-parasite consequence of MTIP dephosphorylation/phosphorylation on invasion not directly measured
    • Kinase responsible for MTIP Ser108 in vivo not pinned down
  12. 2015 Medium

    The signaling hierarchy controlling the motor was incomplete; phosphoproteomics placed PfPKG upstream of CDPK1 and identified actomyosin components including PfMyoA as targets of the PKG-driven cascade required for invasion.

    Evidence Quantitative phosphoproteomics with chemical and conditional-genetic tools in P. falciparum

    PMID:26149123

    Open questions at the time
    • Direct PfMyoA phosphosites attributable to PKG not individually validated
    • Motor activity consequence not measured
  13. 2017 High

    The full light-chain composition and its effect on motor output were unresolved; PfELC was identified as a second light chain that binds the neck/IQ region only after MTIP, and together the two light chains enhance actin velocity to skeletal-actin levels.

    Evidence Recombinant reconstitution, in vitro motility, MS of native complex, hierarchical binding assays in P. falciparum; life-cycle localization and motility in P. berghei

    PMID:28893907 PMID:28978649

    Open questions at the time
    • Structural basis of the two-light-chain lever arm not yet resolved at this stage
    • In-parasite requirement for PfELC not yet tested
  14. 2019 High

    How PfMyoA's atypical sequence and Ser19 phosphorylation tune its mechanics was unknown; three crystal structures plus kinetics showed non-canonical interactions and that Ser19 phosphorylation trades force for speed.

    Evidence X-ray crystallography (three states), steady-state/transient kinetics, in vitro motility, conditional mutagenesis in P. falciparum

    PMID:31337750

    Open questions at the time
    • Full-length motor with both light chains not yet structurally resolved here
    • In vivo kinase controlling Ser19 not defined
  15. 2020 High

    The structural mode of light-chain recognition and the graded functional roles of motor regulation in invasion were unresolved; full-length structures revealed two degenerate IQ motifs engaging PfELC and MTIP, and conditional mutants defined three distinct energetic barriers to RBC invasion requiring active motor.

    Evidence Full-length crystallography in two motor states with MD and kinetics; conditional mutagenesis with live invasion imaging in P. falciparum

    PMID:33046215 PMID:33104759

    Open questions at the time
    • Precise in vivo phosphorylation state during each invasion step not measured
    • How force is transmitted to the RBC membrane not structurally captured
  16. 2021 High

    The atomic interface between PfMyoA and its actin track was undefined; cryo-EM of the rigor-state actomyosin complex showed a conserved core interface plus an ancillary interface positioning the motor on PfAct1.

    Evidence Cryo-EM and atomic model building of the native actomyosin complex in P. falciparum

    PMID:33767187

    Open questions at the time
    • Only the rigor state captured; intermediate powerstroke states not resolved
    • Light-chain region not resolved in this structure
  17. 2022 High

    Whether Ser19 phosphorylation matters for whole-organism motility and transmission was untested; phospho-mutant parasites showed Ser19 phosphorylation controls ookinete gliding, force generation in 3D, and salivary-gland invasion, and higher-resolution cryo-EM resolved both light chains at the neck.

    Evidence Phospho-mutant (S19A/S19D/E6R) parasites with 2D/3D motility, force and transmission assays in P. berghei; high-resolution cryo-EM of the actomyosin complex in P. falciparum

    PMID:35377914 PMID:35506479

    Open questions at the time
    • Sporozoite speed under standard 2D conditions unaffected, leaving stage-specific requirements incompletely explained
    • Kinase/phosphatase dynamics of the Ser19 cycle in vivo not tracked
  18. 2023 High

    Whether PfMyoA is a druggable target was open; KNX-002 was shown to inhibit its ATPase and block blood-stage growth by trapping the motor in a post-rigor state detached from actin via a novel binding mode.

    Evidence In vitro ATPase assay, parasite growth assay, X-ray crystallography of the PfMyoA–inhibitor complex in P. falciparum

    PMID:37308472

    Open questions at the time
    • In vivo efficacy and resistance liability not established
    • Selectivity over host myosins not detailed here

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how the upstream PKG–CDPK1–PKA signaling, MTIP Ser108, and heavy-chain Ser19 phosphorylation events are temporally coordinated at individual invasion steps to switch the motor between force and speed modes in the living parasite.
  • No real-time measurement of PfMyoA phosphorylation states during invasion
  • Phosphatases opposing the regulatory kinases not identified
  • Functional role of the PfDLC1–head interaction unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
CDPK1 (REGULATORY KINASE)GAP40GAP45GAP50MTIP (MLC1)PFACT1 (ACTIN FILAMENTS)PFDLC1 (DYNEIN LIGHT CHAIN 1)PFELC (ESSENTIAL LIGHT CHAIN)PFPKG (UPSTREAM REGULATORY KINASE)PKA (REGULATORY KINASE)RAB11A (VIA MTIP)
Complex memberships
Glideosome motor complex (PfMyoA–MTIP–GAP45–GAP50/GAP40)PfMyoA–MTIP light-chain complexPfMyoA–MTIP–PfELC two-light-chain motorPfMyoA–PfAct1 actomyosin complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PfMyoA (Pfmyo-A / PF3D7_1342600) is synthesized in mature schizonts, present in merozoites, vanishes after erythrocyte entry, is largely associated with the particulate/membrane fraction (not solubilized by agents that dissociate actomyosin or by non-ionic detergent), and localizes by immunofluorescence and immuno-gold EM to the periphery of merozoites/schizonts, concentrated under the plasma membrane adjacent to the outer IMC membrane, with enrichment around the apical prominence. Immunoblot (stage-specificity), subcellular fractionation, immunofluorescence, immuno-gold electron microscopy Journal of cell science Medium 9625746
2000 The 15 amino-acid C-terminal tail domain of PfMyoA (class XIV myosin) is the determinant for peripheral/plasma-membrane localization; truncation abolishes this localization and tight membrane association. Two essential arginine residues in the C-terminal tail are required for plasma-membrane localization, as shown by site-directed mutagenesis. The tail domain is sufficient to confer membrane localization when fused to GFP, and localization is independent of an intact F-actin cytoskeleton. Truncation analysis, site-directed mutagenesis, GFP fusion constructs, subcellular fractionation, immunofluorescence (results primarily demonstrated in TgM-A but the PfM-A sequence was completed and the dibasic motif identified across the class) Molecular biology of the cell Medium 10749937
2003 The 15 amino-acid C-terminal tail domain of PfMyoA specifically interacts with MTIP (myosin A tail domain-interacting protein), as shown by yeast two-hybrid with deletion analysis; the neck domain does not mediate this interaction. In Plasmodium sporozoites, MyoA co-localizes with MTIP at the inner membrane complex (IMC), supporting a model where the tail-anchored MyoA moves actin filaments linked to TRAP-family proteins. Yeast two-hybrid screen with deletion analysis, immunofluorescence co-localization in sporozoites Journal of cell science Medium 12456714
2005 MTIP is expressed in P. falciparum merozoites, localizes to the cell periphery, and forms a stable complex with PfMyoA (Kd ~235 nM). Calcium does not modulate this binding affinity. When the MTIP–MyoA complex is immobilized via anti-MTIP antibodies, PfMyoA drives actin filament movement at 3.51 µm/s, comparable to fast muscle myosins. A peptide derived from the MyoA C-terminal tail (C-MyoA) disrupts the MTIP–MyoA interaction in parasite lysates. Co-immunoprecipitation, surface plasmon resonance (Kd measurement), in vitro actin gliding motility assay, peptide competition assay Journal of molecular biology High 16337961
2005 Homologues of the glideosome motor complex proteins (including GAP45/GAP50/GAP40) are present in P. falciparum merozoites and appear to function in erythrocyte invasion, indicating the same MyoA-based motor complex operates across multiple Plasmodium life-cycle stages. Immunofluorescence, immunoblot, comparative genomics The Journal of biological chemistry Medium 16321976
2006 PfMyoA forms a stable complex with PfMTIP, PfGAP45, and PfGAP50 (the glideosome) in late schizonts and merozoites. PfMyoA interacts with PfMTIP through conserved mechanisms described in other eukaryotes. The glideosome complex is detected by co-immunoprecipitation from parasite lysates. Co-immunoprecipitation, immunofluorescence, immunoblot Molecular and biochemical parasitology Medium 16513191
2006 Crystal structure of Plasmodium MTIP in complex with the PfMyoA tail helix reveals that MTIP undergoes major conformational changes in its C-terminal domain upon binding, creating hydrophobic pockets that receive key hydrophobic side chains of the MyoA tail helix. Three different MTIP conformations were observed in one crystal. The MyoA helix peptide alone can block parasite growth. X-ray crystallography, parasite growth inhibition assay Proceedings of the National Academy of Sciences of the United States of America High 16547135
2007 At neutral pH, the MTIP–PfMyoA complex adopts a compact conformation in which both MTIP domains (D2 and D3) completely surround the MyoA tail helix. Crystallographic and mutagenesis studies show that MyoA residues H810 (unprotonated) and K813 are essential for formation of the compact complex; K813 contacts MTIP with every side-chain atom. X-ray crystallography, site-directed mutagenesis Journal of molecular biology High 17628590
2008 PfCDPK1 phosphorylates MTIP (at Ser47 as the primary site) and GAP45 in vitro. Both proteins are phosphorylated in schizonts. CDPK1 localizes to the periphery of P. falciparum merozoites, suitably positioned to act on motor complex components at the IMC. Kinase inhibitor K252a inhibits both CDPK1 activity and host-cell invasion. In vitro kinase assay, mass spectrometry identification of phosphosites, indirect immunofluorescence, chemical inhibition assay The Journal of biological chemistry High 18768477
2009 Rab11A associates with MTIP (MLC1) and is required for IMC maturation during daughter cell formation. Inducible expression of a MyoA tail-only mutant phenocopies Rab11A ablation, causing an incompletely formed IMC and a block at late cell division, indicating that the MyoA tail (and by extension PfMyoA) is required for completion of cytokinesis/IMC assembly in addition to invasion. Co-immunoprecipitation (Rab11A–MTIP), inducible dominant-negative expression, immunofluorescence PLoS pathogens Medium 19165333
2010 Solution NMR reveals the key determinants of binding at the MTIP/PfMyoA interface; MTIP is highly dynamic and unstable in the absence of the MyoA tail partner. NMR provides the first structural characterization of the complex in solution. Protein NMR (solution structure/dynamics) Molecular bioSystems Medium 20174678
2010 P. falciparum Dynein Light Chain 1 (PfDLC1) binds PfMyoA through the SDIE and/or EEMKT motifs located in the upper 50-kDa segment of the PfMyoA head domain, as shown by interaction studies and co-immunoprecipitation. PfDLC1 co-localizes with PfMyoA in blood-stage parasites. Co-immunoprecipitation, mapping of interacting domains, immunofluorescence co-localization The Journal of biological chemistry Medium 20421304
2011 Stage-specific depletion of PbMyoA in P. berghei ookinetes (via AMA1 promoter swap) completely abolishes ookinete gliding motility and results in a complete block of life-cycle progression in Anopheles mosquitoes, establishing an essential role for MyoA in ookinete motility. Promoter-swap conditional knockdown, gliding motility assay, mosquito transmission assay Cellular microbiology High 21899701
2012 MTIP Ser-107 and/or Ser-108 constitute a phosphorylation hotspot at the MTIP–MyoA interaction interface. Phosphomimetic mutations S108E (and to a lesser extent S107E) break the tight clamp of MTIP around the MyoA tail, as demonstrated by X-ray crystallography, NMR relaxation experiments, and biophysical binding measurements. This is consistent with reduced interaction between recombinant MTIP phosphomimetics and native PfMyoA from parasite lysates, suggesting that phosphorylation of MTIP loosens its grip on PfMyoA. X-ray crystallography, NMR relaxation, biophysical binding assays, pull-down with parasite lysates The Journal of biological chemistry High 22932904
2012 PfMyoA, GAP45, and CDPK1 are substrates of cAMP-dependent protein kinase A (PKA) in P. falciparum schizonts, as confirmed by in vitro kinase assay. This implicates cAMP/PKA signaling as an additional regulator of the glideosome motor complex alongside CDPK1. Quantitative phosphoproteomics, in vitro kinase assay Journal of proteome research Medium 23025827
2015 PfPKG phosphorylates components of the actomyosin complex (including PfMyoA as part of the glideosome), as identified by quantitative global phosphoproteomics with chemical/genetic tools. PfPKG activity is required for parasite invasion, and PfCDPK1 is itself phosphorylated by PfPKG, placing PfPKG upstream of CDPK1 in the signaling cascade that controls the motor complex. Quantitative phosphoproteomics, chemical inhibition, conditional genetic tools Nature communications Medium 26149123
2017 An essential light chain (ELC/PfELC) was identified as a second light chain of PfMyoA, co-purifying with PfMyoA isolated from parasite lysates. PfELC binds the MyoA neck/IQ region adjacent to the MTIP-binding site, and its binding requires MTIP to be already bound to the heavy chain. The presence of both light chains (MTIP and ELC) together enhances PfMyoA-dependent actin filament velocity in motility assays. PfMyoA with both light chains moves PfAct1 filaments at the same speed as skeletal muscle actin. Duty ratio estimates suggest ~9 motors can power actin movement at maximal speed. Baculovirus/Sf9 recombinant protein expression, in vitro actin motility assay, mass spectrometry of parasite-derived complex, light-chain binding hierarchy experiments The Journal of biological chemistry High 28978649
2017 Throughout the P. berghei life cycle, MyoA localizes to the parasite periphery in extracellular ookinetes, sporozoites, and merozoites. In sexual stages, MyoA synthesis occurs only in the developing ookinete protuberance, not in zygotes. In asexual blood stages, MyoA is synthesized in mature schizonts and persists at the merozoite periphery through egress and invasion. The glideosome complex includes GAP40, an additional essential light chain (ELC) binding the MyoA neck, and other candidate components. Co-expression of MyoA with both light chains enhances actin motility. Immunofluorescence (life-cycle staging), in vitro motility assay, co-expression and functional assay The Journal of biological chemistry High 28893907
2019 PfMyoA is critical for red blood cell invasion by P. falciparum. Using X-ray crystallography (three structures in different states), kinetic assays, and in vitro motility assays, PfMyoA was shown to operate via non-canonical interactions. Heavy chain phosphorylation at Ser19 tunes motor properties: unphosphorylated PfMyoA exhibits enhanced ensemble force generation at reduced speed, whereas phosphorylation increases speed. This regulated phosphorylation may optimize PfMyoA for force generation during invasion or fast motility during dissemination. X-ray crystallography (three structural states), steady-state and transient kinetics, in vitro actin motility assay, conditional mutagenesis Nature communications High 31337750
2020 Full-length PfMyoA structures in two states of the motor cycle reveal novel interactions essential for motor priming and show the mode of recognition of two light chains (PfELC and MTIP) by two degenerate IQ motifs. Kinetic and motility assays with PfMyoA variants and molecular dynamics demonstrate how specific priming and atypical sequence adaptations tune mechano-chemical properties. PfELC has an essential role in malaria pathogenesis. X-ray crystallography (full-length, two motor states), kinetics, in vitro motility assays, molecular dynamics simulations eLife High 33046215
2020 Conditional mutagenesis targeting a key PfMyoA phospho-regulation site (Ser19), absence of the PfELC, or complete motor absence each cause distinct stages of incomplete RBC invasion, defining three energetic barriers: RBC deformation (pre-entry), mid-invasion initiation, and completion of internalization. Each barrier requires active PfMyoA motor function. Conditional mutagenesis, live video microscopy, invasion assay PLoS pathogens High 33104759
2021 Cryo-EM structure of the P. falciparum actomyosin complex at the end of the powerstroke (rigor state) shows that the PfMyoA footprint on PfAct1 filaments is conserved with respect to higher eukaryotes despite important sequence variability. The interface contains a conserved core common to all actomyosin complexes and an ancillary interface defining spatial positioning of the motor on actin. Electron cryomicroscopy (cryo-EM), atomic model building Nature communications High 33767187
2022 Phosphorylation of PbMyoA Ser19 increases ookinete gliding motility but does not affect sporozoite speed under standard 2D conditions. S19A mutants show defects in mosquito salivary gland entry. In 3D environments, both S19A and E6R mutations slow ookinetes and salivary gland sporozoites and lower force generation. These data establish that the Ser19 phosphorylation cycle of MyoA influences parasite migration and force generation and is critical for transmission. Phospho-mutant parasite generation (S19A, S19D, E6R), 2D and 3D gliding motility assays, mosquito transmission assay, force measurement EMBO reports High 35506479
2022 High-resolution cryo-EM structure of the P. falciparum actomyosin complex confirms the PfAct1:PfMyoA interface at atomic detail and, at lower resolution, resolves the PfMyoA light-chain binding region accommodating both PfELC and PfMTIP. Electron cryomicroscopy (cryo-EM), high-resolution structure determination PLoS pathogens High 35377914
2023 Small molecule KNX-002 inhibits PfMyoA ATPase activity in vitro and blocks asexual blood stage merozoite growth. X-ray crystallography shows KNX-002 binds PfMyoA using a previously undescribed binding mode, sequestering it in a post-rigor state detached from actin, preventing efficient ATP hydrolysis and lever-arm priming. In vitro ATPase assay, parasite growth assay, X-ray crystallography of PfMyoA–inhibitor complex Nature communications High 37308472

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites. The Journal of biological chemistry 289 16321976
2010 Functional dissection of the apicomplexan glideosome molecular architecture. Cell host & microbe 234 20951968
2003 Myosin A tail domain interacting protein (MTIP) localizes to the inner membrane complex of Plasmodium sporozoites. Journal of cell science 166 12456714
2008 The motor complex of Plasmodium falciparum: phosphorylation by a calcium-dependent protein kinase. The Journal of biological chemistry 147 18768477
2015 Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion. Nature communications 136 26149123
1998 Actomyosin motor in the merozoite of the malaria parasite, Plasmodium falciparum: implications for red cell invasion. Journal of cell science 120 9625746
2012 The Plasmodium falciparum schizont phosphoproteome reveals extensive phosphatidylinositol and cAMP-protein kinase A signaling. Journal of proteome research 112 23025827
2009 Rab11A-controlled assembly of the inner membrane complex is required for completion of apicomplexan cytokinesis. PLoS pathogens 95 19165333
2006 Dual acylation of the 45 kDa gliding-associated protein (GAP45) in Plasmodium falciparum merozoites. Molecular and biochemical parasitology 89 16750579
2000 A dibasic motif in the tail of a class XIV apicomplexan myosin is an essential determinant of plasma membrane localization. Molecular biology of the cell 85 10749937
2006 Plasmodium falciparum erythrocyte invasion: a conserved myosin associated complex. Molecular and biochemical parasitology 84 16513191
2005 The MTIP-myosin A complex in blood stage malaria parasites. Journal of molecular biology 70 16337961
2006 Structure of the MTIP-MyoA complex, a key component of the malaria parasite invasion motor. Proceedings of the National Academy of Sciences of the United States of America 60 16547135
2012 Subcellular location, phosphorylation and assembly into the motor complex of GAP45 during Plasmodium falciparum schizont development. PloS one 55 22479457
2000 Motile systems in malaria merozoites: how is the red blood cell invaded? Parasitology today (Personal ed.) 52 10827429
2011 Tracking Glideosome-associated protein 50 reveals the development and organization of the inner membrane complex of Plasmodium falciparum. Eukaryotic cell 48 21239623
2007 The closed MTIP-myosin A-tail complex from the malaria parasite invasion machinery. Journal of molecular biology 46 17628590
2010 Structure-based design of novel small-molecule inhibitors of Plasmodium falciparum. Journal of chemical information and modeling 44 20426475
2019 Plasmodium myosin A drives parasite invasion by an atypical force generating mechanism. Nature communications 43 31337750
2009 Effects of calcium signaling on Plasmodium falciparum erythrocyte invasion and post-translational modification of gliding-associated protein 45 (PfGAP45). Molecular and biochemical parasitology 43 19576251
2014 Crystal structures of stapled and hydrogen bond surrogate peptides targeting a fully buried protein-helix interaction. ACS chemical biology 40 25084543
2006 Involvement of actin and myosins in Plasmodium berghei ookinete motility. Molecular and biochemical parasitology 38 17028009
2011 Stage-specific depletion of myosin A supports an essential role in motility of malarial ookinetes. Cellular microbiology 36 21899701
2017 Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility. The Journal of biological chemistry 32 28893907
2001 Identification of the class XIV myosins Pb-MyoA and Py-MyoA and expression in Plasmodium sporozoites. Molecular and biochemical parasitology 29 11166399
2019 Systematic analysis of Plasmodium myosins reveals differential expression, localisation, and function in invasive and proliferative parasite stages. Cellular microbiology 27 31283102
2015 The Plasmodium Class XIV Myosin, MyoB, Has a Distinct Subcellular Location in Invasive and Motile Stages of the Malaria Parasite and an Unusual Light Chain. The Journal of biological chemistry 27 25802338
2010 Interaction and dynamics of the Plasmodium falciparum MTIP-MyoA complex, a key component of the invasion motor in the malaria parasite. Molecular bioSystems 27 20174678
2017 Reconstitution of the core of the malaria parasite glideosome with recombinant Plasmodium class XIV myosin A and Plasmodium actin. The Journal of biological chemistry 25 28978649
2019 Unusual dynamics of the divergent malaria parasite PfAct1 actin filament. Proceedings of the National Academy of Sciences of the United States of America 24 31548388
2015 Inhibition by stabilization: targeting the Plasmodium falciparum aldolase-TRAP complex. Malaria journal 23 26289816
2021 The actomyosin interface contains an evolutionary conserved core and an ancillary interface involved in specificity. Nature communications 22 33767187
2020 Full-length Plasmodium falciparum myosin A and essential light chain PfELC structures provide new anti-malarial targets. eLife 22 33046215
2020 Actomyosin forces and the energetics of red blood cell invasion by the malaria parasite Plasmodium falciparum. PLoS pathogens 22 33104759
2014 Targeting a dynamic protein-protein interaction: fragment screening against the malaria myosin A motor complex. ChemMedChem 20 25367834
2012 Regulation of the Plasmodium motor complex: phosphorylation of myosin A tail-interacting protein (MTIP) loosens its grip on MyoA. The Journal of biological chemistry 20 22932904
2020 Structural role of essential light chains in the apicomplexan glideosome. Communications biology 17 33051581
2005 Plasmodium falciparum myosins: transcription and translation during asexual parasite development. Cell motility and the cytoskeleton 17 15754360
2000 Myosin A expressions in sporogonic stages of Plasmodium. Molecular and biochemical parasitology 16 11163454
2022 High-resolution structures of malaria parasite actomyosin and actin filaments. PLoS pathogens 15 35377914
2010 Plasmodium falciparum dynein light chain 1 interacts with actin/myosin during blood stage development. The Journal of biological chemistry 15 20421304
2013 The structure of the D3 domain of Plasmodium falciparum myosin tail interacting protein MTIP in complex with a nanobody. Molecular and biochemical parasitology 14 23831371
2023 Mechanism of small molecule inhibition of Plasmodium falciparum myosin A informs antimalarial drug design. Nature communications 13 37308472
2022 Phosphorylation of myosin A regulates gliding motility and is essential for Plasmodium transmission. EMBO reports 13 35506479
2016 Production of recombinant proteins from Plasmodium falciparum in Escherichia coli. Biomedica : revista del Instituto Nacional de Salud 12 27622630
2020 Peptide Probes for Plasmodium falciparum MyoA Tail Interacting Protein (MTIP): Exploring the Druggability of the Malaria Parasite Motor Complex. ACS chemical biology 10 32383851
2020 A De novo Peptide from a High Throughput Peptide Library Blocks Myosin A -MTIP Complex Formation in Plasmodium falciparum. International journal of molecular sciences 7 32859024
2013 The compact conformation of the Plasmodium knowlesi myosin tail interacting protein MTIP in complex with the C-terminal helix of myosin A. Molecular and biochemical parasitology 6 23831369
2020 Targeting Plasmodium with constrained peptides and peptidomimetics. IUBMB life 5 32037730
2018 Systematic Comparison of Strategies to Achieve Soluble Expression of Plasmodium falciparum Recombinant Proteins in E. coli. Molecular biotechnology 5 30259259
2000 Isolation and identification of actin-binding proteins in Plasmodium falciparum by affinity chromatography. Memorias do Instituto Oswaldo Cruz 5 10800190
2017 Myosin B of Plasmodium falciparum (PfMyoB): in silico prediction of its three-dimensional structure and its possible interaction with MTIP. Parasitology research 4 28265752
2024 The novel Plasmodium berghei protein S14 is essential for sporozoite gliding motility and infectivity. Journal of cell science 3 38832798
2019 Polarization of MTIP is a signature of gliding locomotion in Plasmodium ookinetes and sporozoites. Molecular and biochemical parasitology 3 31874192
2018 In vitro interaction between Plasmodium falciparum myosin B (PfMyoB) and myosin A tail interacting protein (MTIP). Parasitology research 2 30094538
2022 Complementary crosstalk between palmitoylation and phosphorylation events in MTIP regulates its role during Plasmodium falciparum invasion. Frontiers in cellular and infection microbiology 1 36250062
2025 Bilaterally Substituted Terphenyl Molecules Efficiently Inhibit the Interaction between a Protein and a Fully Buried α-Helix in the Malaria Parasite Motor System. Journal of the American Chemical Society 0 40316890
2002 [Preparation of DNA libraries of Plasmodium falciparum for searching calmodulin binding protein genes, GOGAT and Pfmyo A]. Biomedica : revista del Instituto Nacional de Salud 0 12404924