Structural Insights into Functional Overlapping and Differentiation among Myosin V Motors

• Grant number: 13/22098-2
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: December 01, 2013
• End date: May 31, 2014
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Mário Tyago Murakami
• Grantee: Mário Tyago Murakami
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Myosin V (MyoV) motors have been implicated in the intracellular transport of diverse cargoes including vesicles, organelles, RNA-protein complexes, and regulatory proteins. Here,we have solved the cargo-binding domain (CBD) structures of the three human MyoV paralogs (Va, Vb, and Vc), revealing subtle structural changes that drive functional differentiation and anovel redox mechanism controlling the CBD dimerization process, which is unique for the MyoVc subclass. Moreover, the cargo- and motor-binding sites were structurally assigned, indicating the conservation of residues involved in the recognition of adaptors for peroxisome transport and providing high resolution insights into motor domain inhibition by CBD. These results contribute to understanding the structural requirements for cargo transport, autoinhibition, and regulatory mechanisms in myosin V motors. (AU)