Functional specificity conferred by the unique plasticity of fully α‐helical Ras and Rho GAPs

FEBS Letters

Bril, Antoine²  Poupon, Anne³  Souchet, Michel²  Calmels, Thierry P.G.²  Léger, Isabelle²  Mornon, Jean-Paul¹  Callebaut, Isabelle¹ 

[1] Systèmes moléculaires et Biologie structurale, LMCP, CNRS UMR C7590, UP6, Case 115, 4 Place Jussieu, 75252 Paris Cedex 05, France;SmithKline Beecham Laboratoires Pharmaceutiques, 4 rue Chesnay-Beauregard, 35760 Saint-Grégoire, France;Département d'Ingénierie et d'Etude des Protéines, Bat. 152, CEA/Saclay, 91191 Gif sur Yvette Cedex, France

关键词: Four-helix bundle;    Plasticity;    GTPase activating protein;    Ras;    Rho;   

DOI  :  10.1016/S0014-5793(00)01769-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown