Understanding the role of phosphorylation cargo binding domain (CBD) in the regulation of unconventional myosins Class V

Abstract

Myosins are motor proteins that use ATP hydrolysis energy to move on actin filaments in the cytoskeleton. Divided into at least 35 classes, myosins are involved in diverse intracellular functions such as muscle contraction, cargo transport and cytoskeletal reorganization. The unconventional myosin class V (MyoV), particularly active in the transport of organelles, vesicles and mRNA. In humans, three paralogous genes (MYO5A , MYO5b and MYO5c) encoding this myosin class. Structurally, MyoV can be divided into four domains: a motor domain that binds to actin and is responsible for its processivity, a neck domain, with 6 IQ motifs (calmodulin binding) to a coiled -coil domain responsible for dimerization of the molecule and a cargo binding domain (CBD). Besides acting in the recognition of molecular cargoes, the CBD has a fundamental role in the mechanism of inhibition of motor domain activity through interactions favored by a large conformational change. When phosphorylated on one of the loops of CBD, the MyoVa is found in subnuclear compartments being redistributed to the nucleolus once inhibited transcription. However, the conformational changes resulting from this phosphorylation and its role in regulating the function MyoVa are still poorly understood. Thus, this project aims to contribute to a better understanding of the role of phosphorylation in CBD in regulating the formation of the inhibited state MyoV, as the specificity of recognition of loads. (AU)