1.9A Crystal Structure of the Rap1a GTPase Bound to its Natural Ligand, GTP

Abstract

Rap1a is a small GTPase in the Ras superfamily whose most well known function is to antagonize the Ras. Rap1a and Ras share common effectors which allow Rap1a to either unproductively bind Ras' effectors forming an inactive complex or sequester Ras' effectors away from the plasma membrane where Ras is inserted by C-terminal post-translational modifications. To date, a 2.2Å crystal structure of Rap1a bound to the non-hydrolyzable GTP analogue, GMPPNP, and one of its effectors, Raf-1, has been solved. This thesis presents the 1.9Å monomeric form of Rap1a bound to its natural ligand, GTP. Comparisons made between the previously published Rap—Raf structure, Rap2a, H-Ras, and RalA shed some light on the functions for conserved areas of Rap1a. The presence of a unique salt bridge at the Rap⁄Raf interface, a new conformation of threonine 61, a possible link for switch the II residue phenylalanine 64 with GAP-induced GTPase activity, and a suggested role for α helix 4 contribute to the Rap1a story.