Structural study of the Cdc25 domain from Ral-specific guanine-nucleotide exchange factor RalGPS1a

作     者：Wei Peng Jiwei Xu Xiaotao Guan Yao Sun Xuejun C.Zhang Xuemei Li Zihe Rao 

作者机构：National Laboratory of BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2011年第2卷第4期

页      面：308-319页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 0836[工学-生物工程] 

基　　金：the State Key Development Program for Basic Research of the Ministry of Science and Technology of China(973 Project)(Grant Nos.2007CB914304,2011CB915501,and 2011CB910304) the National High Technology Research and Development Program of China(863 Project)(Grant No.2006AA02A322) National Key Technologies R&D Program(Grant No.2009ZX10603)of the Ministry of Health of China 

主　　题：RalGPS1a RalA cdc25 domain crystal structure 

摘      要：The guanine-nucleotide exchange factor(GEF)RalGPS1a activates small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP,thus regulating various downstream cellular ***1a is composed of an Nterminal Cdc25-like catalytic domain,followed by a PXXP motif and a C-terminal pleckstrin homology(PH)*** Cdc25 domain of RalGPS1a,which shares about 30%sequence identity with other Cdc25-domain proteins,is thought to be directly engaged in binding and activating the substrate Ral *** we report the crystal structure of the Cdc25 domain of *** bowl shaped structure is homologous to the Cdc25 domains of SOS and *** most remarkable difference between these three Cdc25 domains lies in their active sites,referred to as the helical hairpin *** with previous enzymological studies,the helical hairpin of RalGPS1a adopts a conformation favorable for substrate binding.A modeled RalGPS1a-RalA complex structure reveals an extensive binding surface similar to that of the SOS-Ras ***,analysis of the electrostatic surface potential suggests an interaction mode between the RalGPS1a active site helical hairpin and the switch 1 region of substrate RalA distinct from that of the SOS-Ras complex.