Key result
Crystal structures of MyoVa-GTD reveal two distinct cargo-binding surfaces, providing a framework for understanding cargo recognition mechanisms of vertebrate class V myosins.
The resolved MyoVa-GTD structures provide a framework for understanding cargo recognition mechanisms and the impact of disease-associated mutations in vertebrate class V myosins.
May aid interpretation of myosin mutations; leaves open effects on vertebrate cardiac function.
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.
No takes yet. Share an insight, caveat, or question.
Wei et al. (2013) studied this question. Crystal structures of MyoVa-GTD reveal two distinct cargo-binding surfaces, providing a framework for understanding cargo recognition mechanisms of vertebrate class V myosins.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: