Structure of the MTIP-MyoA complex, a key component of the malaria parasite invasion motor.
The causative agents of malaria have developed a sophisticated machinery for entering multiple cell types in the human and insect hosts. In this machinery, a critical interaction occurs between the unusual myosin motor MyoA and the MyoA-tail Interacting Protein (MTIP). Here we present one crystal structure that shows three different conformations of Plasmodium MTIP, one of these in complex with the MyoA-tail, which reveal major conformational changes in the C-terminal domain of MTIP upon binding the MyoA-tail helix, thereby creating several hydrophobic pockets in MTIP that are the recipients of key hydrophobic side chains of MyoA. Because we also show that the MyoA helix is able to block parasite growth, this provides avenues for designing antimalarials.
Bosch
Jürgen
J
Department of Biochemistry and Biological Structure, University of Washington, Seattle, WA 98195, USA.
Turley
Stewart
S
Daly
Thomas M
TM
Bogh
Stephen M
SM
Villasmil
Michelle L
ML
Roach
Claudia
C
Zhou
Na
N
Morrisey
Joanne M
JM
Vaidya
Akhil B
AB
Bergman
Lawrence W
LW
Hol
Wim G J
WG
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D020409:Molecular Motor Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009218:Myosins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010961:Plasmodium / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D020798:Two-Hybrid System Techniques
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D020409:Molecular Motor Proteins; D021122:Protein Subunits; D015800:Protozoan Proteins; D009218:Myosins