Structural and functional studies of molecular mechanisms involved in the recognition and interaction of myosin XI with cellular cargoes

Abstract

The unconventional myosins play an important role in several physiological processes such as intracellular traffic of organelles, vesicles and RNA; cytoplasmic streaming; cellular shape; maintenance of cell architecture; signal transduction and morphogenesis. These molecular motors have a sophisticated mechanochemical mechanism and their regulation and specificity involve conformational changes and coupling with co-transporters proteins. Although some aspects of myosins XI have been extensively investigated including their kinetics, mechanical properties and intracellular functions, little is known about their three-dimensional structure and molecular partners as well as the mechanisms governing the recognition and binding of these adaptors to the cargo-binding domain.Therefore, the aim of this research project is to characterize functionally and structurally the globular tail (cargo-binding domain) of myosins XI from the model organism Arabidopsis thaliana using a multidisciplinary approach, which includes molecular biology techniques (yeast two-hybrid system) and biophysical methods (X-ray crystallography, small-angle X-ray scattering and spectroscopy). In this sense, we expect to advance in the basic knowledge about the function and regulation of these molecular motors. Moreover, given the high sequence similarity with class V myosins, the myosins XI from plant is an instrumental model to understand the role of these proteins in higher eukaryotes. It is worth mentioning that the knowledge derived from this project could be useful for developing breeding programs of plants with agronomic relevance. (AU)