Sequence and 3D structural relationships between mammalian Ras‐ and Rho‐specific GTPase‐activating proteins (GAPs): the cradle fold

FEBS Letters

Bril, Antoine²  Durand, Patrick¹  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

关键词: Ras;    Rho;    GAP;    HCA;    3D structure;   

DOI  :  10.1016/S0014-5793(98)00331-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

An extensive study of both sequence and recent 3D structural data concerning GTPase interacting domains of Ras- and Rho-specific GTPase-activating proteins (GAPs) shows that these two subfamilies share a same 3D scaffold and are thus related to each other. This relationship has heretofore remained undetected although these domains of similar size are both totally α-helical and activate nearly structurally identical targets (Ras and Rho proteins). In this report, sequence similarities correlated to 3D structures of p120rasGAP and p50rhoGAP were detected using the sensitive two-dimensional method hydrophobic cluster analysis (HCA). These patterns were further extended to other members in each subfamily and the geometry orientation of crucial arginines R789 in p120 and R282 in p50 and of important stabilizing residues like p120R903 and p50N391 was confirmed. This overall structural relationship is centered on an invariant motif of three consecutive helices that we suggest to name the ‘cradle fold’. This observation opens new perspectives to understand how small GTPases are specifically regulated.

【 授权许可】

Unknown