Cycling and Regulation of the G-Proteins NOEY2 and Rig.

Suny At Stony Brook, Stony Brook NY

Investigators

Abstract

GTP-binding proteins are essential components of cellular pathways that relay extracellular signals to gene expression and changes in cell shape. Cycling of GTP-binding proteins between an active and inactive form is required for normal cell growth, cell differentiation, cell-cell communication, nuclear transport and other important cellular functions. Disruption of their normal activity by amino acid substitution results in uncontrolled cell growth and transformation. This research focuses on understanding the role of two newly identified GTP-binding proteins, Rig and NOEY2, which suppress cellular growth and transformation. X-ray crystallography will be used to determine the three-dimensional structures of the active and inactive forms of these two proteins. To probe the reaction of GTP-hydrolysis, molecular dynamics simulations will be used to generate the coordinates of various structure intermediates along the reaction path. The simulations will be validated by mutating residues shown to play critical roles during GTP-hydrolysis. More broadly, this project is conceived with two goals in mind: to better our understanding of an important family of proteins and to strengthen graduate and undergraduate education. This research will allow graduate and undergraduate students to participate in the design and execution of the various experiments. It will provide them with an opportunity to write and coauthor scientific publications. It will also allow them to see first hand how different biophysical techniques are in synergy to answer an important biological question.