title: The MTIP-myosin A complex in blood stage malaria parasites.
abstract: Parasites of the Apicomplexa phylum use an actomyosin motor to drive invasion of host cells. The motor complex is located at the parasite's periphery between the plasma membrane and an inner membrane complex. A crucial component of this complex is myosin tail domain interacting protein (MTIP) identified in the murine malaria parasite Plasmodium yoelii. Here, we show that MTIP is expressed in Plasmodium falciparum merozoites, localises to the periphery of the cell and is present in a complex with myosin A. The MTIP-myosin A tail interaction has a Kd of 235 nM and calcium ions do not play a role in modulating the binding affinity of the two molecules, despite reports of a predicted EF-hand in MTIP. Antibodies to MTIP were used to immobilise the MTIP-myosin A complex, allowing actin binding and motility to be examined. Measurement of actin filament velocities powered by myosin A revealed a velocity of 3.51 microm s(-1), a speed comparable to fast muscle myosins. A short peptide derived from the tail of myosin A (C-MyoA) bound to MTIP and was able to disrupt the association of MTIP and myosin A in parasite lysates. C-MyoA peptidomimetic compounds that disrupt the MTIP-myosin A interaction are predicted to inhibit parasite motility and host cell invasion, which may be targets for new therapeutic approaches.
authors.affiliation: Division of Parasitology, MRC National Institute for Medical Research, London NW7 1AA, UK. judith.green@nimr.mrc.ac.uk
authors.forename: Judith L
authors.initials: JL
authors.lastname: Green
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Martin
authors.forename: Jeremy
authors.initials: J
authors.lastname: Fielden
authors.forename: Asimina
authors.initials: A
authors.lastname: Ksagoni
authors.forename: Munira
authors.initials: M
authors.lastname: Grainger
authors.forename: Brian Y S
authors.initials: BY
authors.lastname: Yim Lim
authors.forename: Justin E
authors.initials: JE
authors.lastname: Molloy
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
mesh_terms: D000818:Animals; D001769:Blood / Q000469:parasitology*; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C477148:MTIP protein, Plasmodium yoelii; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D015800:Protozoan Proteins; D024507:Nonmuscle Myosin Type IIA; D002118:Calcium