Structural and functional characterization of the phosphorylation effects on the globular tail domain of human myosin Va

Abstract

The myosins V (MyoV) constitute a class of protein homodimers capable of converting chemical energy into movement through actin filaments. They play a key role in many essential cellular processes and, together with their molecular partners, are responsible for the intracellular transport of vesicles, organelles, proteins, and mRNA. Some studies point out that Ser1652 residue phosphorylation, located at a long flexible loop (phospho-loop) of the globular tail domain of the human MyoVa (GTD-MyoVa), has an important regulatory role in cell cycle control and nuclear localization. However, since the structure of phosphorylated GTD has not been solved yet, both structural and functional implications of this covalent modification remain unknown. We believe phospho-loop might interact with positive charged nearby regions, potentially disrupting MyoVa auto-inhibition conformation and its capacity to recognize molecular partners, such as Rab-11.In order to shed light on Ser1652 phosphorylation effects for this protein class, we intend to solve the structure of the phosphomimetic GTD-MyoVa mutant using X-ray crystallography and analyze phosphorylation impacts on Rab-11/GTD-MyoVa interaction.(AU)