Abstract
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.
Publication types
- Research Support, N.I.H., Extramural
MeSH terms
- Amino Acid Sequence
- Animals
- Conserved Sequence
- Cytoskeletal Proteins / chemistry
- Cytoskeletal Proteins / genetics
- Cytoskeletal Proteins / metabolism*
- Hydrophobic and Hydrophilic Interactions
- Membrane Proteins / chemistry
- Membrane Proteins / genetics
- Membrane Proteins / metabolism*
- Models, Molecular
- Molecular Motor Proteins
- Molecular Sequence Data
- Mutation
- Myosins / chemistry
- Myosins / genetics
- Myosins / metabolism*
- Plasmodium / chemistry*
- Plasmodium / genetics
- Plasmodium / physiology*
- Protein Binding
- Protein Structure, Quaternary
- Protein Subunits / chemistry
- Protein Subunits / genetics
- Protein Subunits / metabolism
- Protozoan Proteins / chemistry*
- Protozoan Proteins / genetics
- Protozoan Proteins / metabolism*
- Sequence Alignment
- Two-Hybrid System Techniques
Substances
- Cytoskeletal Proteins
- Membrane Proteins
- Molecular Motor Proteins
- Protein Subunits
- Protozoan Proteins
- Myosins