Functional specificity conferred by the unique plasticity of fully alpha-helical Ras and Rho GAPs

Structural comparisons of the two GTPase activating proteins (GAPs) p120 an d p50 in complex with Pas and Rho, respectively, allowed us to decipher the functional role of specific structural features, such as helix alpha 8c of p120 and helix A1 of p50, necessary for small GTPase recognition. We ident ified important residues that may be critical for stabilization of the GAP/ GTPase binary complexes, Detection of topohydrophobic positions (positions which are most often occupied by hydrophobic amino acids within a family of protein domains) conserved between the two GAP families led to the charact erization of a common flexible four-helix bundle. Altogether, these data ar e consistent with a rearrangement of several helices around a common core, which strongly supports the assumption that p50 and p120 GAPs derive from a unique fold. Considered as a whole, the remarkable plasticity of GAPs appe ars to be a means used by nature to accurately confer functional specificit y. (C) 2000 Federation of European Biochemical Societies, Published by Else vier Science B.V. All rights reserved.