The charge-dipole pocket: a Ras-like GTPase component associated with switch II restructuring
October 7, Tue 2008
1:00 pm, MRB 200 Conference Room
Dr. Andrew Neuwald
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine
Ras-like GTPases, which include the Rab, Ran, Rho, Ras, Arf, Sar and GÎ± families, function as on-off switches in intracellular signaling pathways. Using a statistically-based iterative strategy, a quarter of a million GTPase sequences were multiply-aligned and then optimally partitioned into subgroups based on amino acid differences at evolutionarily-divergent residue positions. One outcome of this analysis is the identification of a previously undescribed structural component among the molecular features that most distinguish Ras-like GTPases from other GTPases. This component forms a pocket around the negative-dipole moment at the end of a switch II Î±-helix with a positively-charged residue inserted into this pocket. This helix is oriented in a specific direction away from the GTPase core, but is dramatically altered upon disruption of the charge-dipole pocket, which thus appears to perform a switch II restructuring role.