Structure of the MTIP-MyoA Complex, a Key Component of the Malaria Parasite Invasion Motor

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 13; pp. 4852 - 4857
• Main Authors: Bosch, Jürgen, Turley, Stewart, Daly, Thomas M., Bogh, Stephen M., Villasmil, Michelle L., Roach, Claudia, Zhou, Na, Morrisey, Joanne M., Vaidya, Akhil B., Bergman, Lawrence W., Hol, Wim G. J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 28.03.2006; National Acad Sciences
• Subjects: Amino Acid Sequence; Animals; Atoms; BASIC BIOLOGICAL SCIENCES; Biochemistry; Biological Sciences; Biology; Cell membranes; COMPLEXES; Conserved Sequence; Crystal structure; Crystals; Cytoskeletal Proteins - chemistry; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Hepatocytes; Hydrophobic and Hydrophilic Interactions; MALARIA; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Models, Molecular; Molecular Motor Proteins; Molecular Sequence Data; MORPHOLOGY; Mutation; Myosins - chemistry; Myosins - genetics; Myosins - metabolism; Other,OTHER; Parasite hosts; PARASITES; Parasitism; Plasmodium; Plasmodium - chemistry; Plasmodium - genetics; Plasmodium - physiology; Protein Binding; Protein Structure, Quaternary; Protein Subunits - chemistry; Protein Subunits - genetics; Protein Subunits - metabolism; Proteins; Protozoan Proteins - chemistry; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Sequence Alignment; Two-Hybrid System Techniques; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0510907103

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.