title: Regulation of the Plasmodium motor complex: phosphorylation of myosin A tail-interacting protein (MTIP) loosens its grip on MyoA.
abstract: The interaction between the C-terminal tail of myosin A (MyoA) and its light chain, myosin A tail domain interacting protein (MTIP), is an essential feature of the conserved molecular machinery required for gliding motility and cell invasion by apicomplexan parasites. Recent data indicate that MTIP Ser-107 and/or Ser-108 are targeted for intracellular phosphorylation. Using an optimized MyoA tail peptide to reconstitute the complex, we show that this region of MTIP is an interaction hotspot using x-ray crystallography and NMR, and S107E and S108E mutants were generated to mimic the effect of phosphorylation. NMR relaxation experiments and other biophysical measurements indicate that the S108E mutation serves to break the tight clamp around the MyoA tail, whereas S107E has a smaller but measurable impact. These data are consistent with physical interactions observed between recombinant MTIP and native MyoA from Plasmodium falciparum lysates. Taken together these data support the notion that the conserved interactions between MTIP and MyoA may be specifically modulated by this post-translational modification.
authors.affiliation: Institute of Chemical Biology, Imperial College London, SW7 2AZ, United Kingdom.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Douse
authors.forename: Judith L
authors.initials: JL
authors.lastname: Green
authors.forename: Paula S
authors.initials: PS
authors.lastname: Salgado
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Simpson
authors.forename: Jemima C
authors.initials: JC
authors.lastname: Thomas
authors.forename: Gordon
authors.initials: G
authors.lastname: Langsley
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cota
mesh_terms: D019943:Amino Acid Substitution; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004055:Differential Thermal Analysis; D004912:Erythrocytes / Q000469:parasitology; D005470:Fluorometry; D006801:Humans; D008958:Models, Molecular; D024507:Nonmuscle Myosin Type IIA / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D017186:Titrimetry
chemical_list: D003598:Cytoskeletal Proteins; D015800:Protozoan Proteins; D024507:Nonmuscle Myosin Type IIA