MyoB

MyoB (PF3D7_0503600) is a class XIV myosin motor of Plasmodium expressed in all invasive stages—merozoites, ookinetes, and sporozoites—that occupies a discrete position at the extreme apical tip, anterior to and distinct from rhoptries, rhoptry-neck proteins, and micronemes (PMID:25802338). Unlike the glideosome motor MyoA, MyoB is not associated with glideosome components including the MyoA light chain MTIP, marking it as a mechanistically separate apical motor (PMID:25802338). MyoB partners with a dedicated, essential light chain, MLC-B, which carries a C-terminal calmodulin-like domain and co-localizes with MyoB at the apical pole to form a specific complex (PMID:25802338, PMID:31283102). Reconstitution of recombinant MyoB with the parasite chaperones Hsp90 and Unc45 demonstrated that it is a bona fide motor: it binds actin with high affinity, has actin-activated ATPase activity, and drives actin-filament motility in vitro, with ADP release faster than the overall ATP turnover; SAXS confirmed an overall myosin shape (PMID:36273584). Functionally, MyoB is non-essential for survival, but its loss delays the initial stages of red blood cell invasion and produces a growth defect correlated with reduced invasion success, consistent with a role as an auxiliary invasion motor at the apical tip (PMID:33104759, PMID:36273584). Expression of MyoB is post-transcriptionally controlled, with transcript present through asexual development but protein restricted to late schizogony (PMID:15754360).

1. 2005 Medium

   Establishing when MyoB protein is made addressed whether its abundant transcript reflects constitutive activity or staged deployment, revealing translational control that times the motor to the invasive phase.

   Evidence RT-PCR for transcript plus protein detection across asexual blood stages in P. falciparum

   PMID:15754360

   Open questions at the time

   • Mechanism of translational repression/derepression not identified
   • Does not address MyoB localization or partners
2. 2006 Medium

   Comparing MyoB and MyoA distribution in ookinetes tested whether MyoB simply mirrors the known apical motor, and instead showed a distinct peripheral, earlier-expressed pattern, hinting at a separate role.

   Evidence Western blot and immunofluorescence across ookinete development in P. berghei

   PMID:17028009

   Open questions at the time

   • Single species and single lab
   • Peripheral pattern in ookinetes not reconciled with later apical-tip localization in merozoites
   • No functional readout
3. 2015 High

   Determining MyoB's precise location and binding partners answered whether it belongs to the glideosome, establishing it as a glideosome-independent apical-tip motor with its own dedicated light chain MLC-B.

   Evidence Immunofluorescence, reciprocal co-immunoprecipitation, and Western blot across P. falciparum, P. berghei, and P. knowlesi

   PMID:25802338

   Open questions at the time

   • Functional consequence of apical localization not tested
   • Whether MLC-B is the only physiological light chain unresolved
4. 2018 Low

   An in vitro binding test asked whether the MyoA light chain MTIP could also serve MyoB, reporting a recombinant interaction that stands in tension with the native co-IP showing no glideosome association.

   Evidence Far Western and in vitro competition/inhibition assays with recombinant proteins in P. falciparum

   PMID:30094538

   Open questions at the time

   • In vitro only, not confirmed in native parasite
   • Directly conflicts with the negative co-IP result for MTIP association [#3]
   • Physiological relevance unknown
5. 2019 High

   Gene deletion asked whether MyoB is required for the parasite, showing it is dispensable for survival while confirming MLC-B is essential and temporally offset from MyoB in ookinetes.

   Evidence Gene knockout with life-cycle immunofluorescence and Western blot in P. berghei

   PMID:31283102

   Open questions at the time

   • Why MLC-B is essential while MyoB is not is unexplained
   • Temporal mismatch between MyoB and MLC-B expression not mechanistically resolved
6. 2020 Medium

   Conditional removal of parasite motors during invasion tested where motor force is needed, defining three energetic barriers and placing MyoB as an auxiliary motor in RBC invasion.

   Evidence Conditional mutagenesis with live video microscopy of invasion in P. falciparum

   PMID:33104759

   Open questions at the time

   • MyoB's specific contribution inferred from combined motor-absence experiments rather than isolated
   • Which barrier MyoB acts on not separately resolved
7. 2022 High

   In vitro reconstitution and a targeted knockout together answered whether MyoB is a genuine functional motor and what its loss costs, showing actin-activated motor activity and an invasion-stage delay/growth defect upon deletion.

   Evidence Recombinant MyoB with Hsp90/Unc45 chaperones, ATPase and actin-gliding assays, kinetics, light-chain and actin binding, SAXS; plus knockout with growth/invasion assays and immunofluorescence in P. falciparum

   PMID:36273584

   Open questions at the time

   • High-resolution structure not determined (only low-resolution SAXS)
   • The in vivo cargo or tethering substrate at the apical tip not identified
   • Roles of the four additional IQ2-binding candidate light chains untested in vivo

• The precise mechanical role of MyoB at the apical tip during invasion—whether it senses force, tethers, or generates directional force, and against which substrate—remains undefined.
• No identified in vivo binding partner beyond MLC-B and actin
• Molecular basis of the invasion delay phenotype unresolved
• Physiological light-chain composition of the native complex unconfirmed