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Functional specificity conferred by the unique plasticity of fully α‐helical Ras and Rho GAPs
Author(s) -
Souchet Michel,
Poupon Anne,
Callebaut Isabelle,
Léger Isabelle,
Mor Jean-Paul,
Bril Antoine,
Calmels Thierry P.G.
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01769-5
Subject(s) - gtpase , helix (gastropod) , biology , helix bundle , gtpase activating protein , bridging (networking) , protein structure , computational biology , microbiology and biotechnology , biophysics , genetics , evolutionary biology , biochemistry , signal transduction , g protein , ecology , computer science , computer network , snail
Structural comparisons of the two GTPase activating proteins (GAPs) p120 and p50 in complex with Ras and Rho, respectively, allowed us to decipher the functional role of specific structural features, such as helix α8c of p120 and helix A1 of p50, necessary for small GTPase recognition. We identified 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 characterization of a common flexible four‐helix bundle. Altogether, these data are 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 appears to be a means used by nature to accurately confer functional specificity.