Doctor Ioan Kosztin
Beckman Institute
University of Illinois at Urbana-Champaign
Urbana, Illinois

Monday, February 5, 2001
3:00 pm (CT)
3269 Beckman Institute

Abstract

G-proteins function as molecular signaling switches and play a critical role in many essential signal transduction processes such as cell growth and differentiation. They are also involved in many malignancies. Switching is induced by GTP->GDP hydrolysis and cycle between a GTP-bound active state and a GDP-bound inactive state, the switching between these two states being regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). The GTP binding site in G-proteins shows a remarkable architectural similarity to the ATP binding site of motor proteins, the latter generating force through ATP->ADP hydrolysis. This suggests a common mechanism between motor and signaling proteins, i.e., that the latter generate a force relevant to the switching process. Molecular dynamics simulation have described in detail the structural transformation that occurs after GTP hydrolysis in H-Ras, the smallest known G-protein. The results suggest an ``order-disorder'' transition between an initial tense (T) and final relaxed (R) state of H-Ras that is actually accompanied by force-generation in a crucial protein segment. The force can play a significant role in the signaling cycle of Ras, i.e., in the interaction with proteins GAP and GEF, and should be detectable by atomic force microscopy.

Tea and coffee will be served in R3151 Beckman Institute at 2:15pm.