Structural basis of cargo recognitions for class V myosins.

Abstract

Class V myosins (MyoV), the most studied unconventional myosins, recognize numerous cargos mainly via the motor's globular tail domain (GTD). Little is known regarding how MyoV-GTD recognizes such a diverse array of cargos specifically. Here, we solved the crystal structures of MyoVa-GTD in its apo-form and in complex with two distinct cargos, melanophilin and Rab interacting lysosomal protein-like 2. The apo-MyoVa-GTD structure indicates that most mutations found in patients with Griscelli syndrome, microvillus inclusion disease, or cancers or in "dilute" rodents likely impair the folding of GTD. The MyoVa-GTD/cargo complex structure reveals two distinct cargo-binding surfaces, one primarily via charge-charge interaction and the other mainly via hydrophobic interactions. Structural and biochemical analysis reveal the specific cargo-binding specificities of various isoforms of mammalian MyoV as well as very different cargo recognition mechanisms of MyoV between yeast and higher eukaryotes. The MyoVa-GTD structures resolved here provide a framework for future functional studies of vertebrate class V myosins.

• Authors: Zhiyi Wei, Xiaotian Liu, Cong Yu, Mingjie Zhang
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 110 Issue 28 Pg. 11314-9 (Jul 09 2013) ISSN: 1091-6490 [Electronic] United States
• PMID: 23798443 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Myosins

Topics

• Amino Acid Sequence
• Binding Sites
• Models, Molecular
• Molecular Sequence Data
• Mutation
• Myosins (chemistry, genetics)
• Protein Conformation
• Sequence Homology, Amino Acid