Catalytic competence of the Ras-GEF domain of hSos1 requires intra-REM domain interactions mediated by phenylalanine 577

被引:8
作者
Sacco, Elena [1 ]
Metalli, David [1 ]
Busti, Stefano [1 ]
Fantinato, Sonia [1 ]
D'Urzo, Annalisa [1 ]
Mapelli, Valeria [1 ]
Alberghina, Lilia [1 ]
Vanoni, Marco [1 ]
机构
[1] Univ Milan, Dipartimento Biotecnol & Biosci, I-20126 Milan, Italy
关键词
guanine nucleotide exchange factor; biacore; catalytic region; mutagenesis; intramolecular interaction;
D O I
10.1016/j.febslet.2006.10.040
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Ras-specific guanine nucleotide exchange region of hSos1 consists of two consecutive domains: the catalytic core (residues 742-1024) contains all residues binding to Ras, including the catalytic hairpin, and an upstream REM domain (residues 553-741), so called because it contains an evolutionary conserved Ras Exchange Motif (REM). We functionally define the boundaries of the REM domain through a combination of in vivo and in vitro assays. We show that an intra-REM domain interaction, mediated by phenylalanine 577, is required to allow interaction of the REM domain with the catalytic core, constraining it in the active conformation. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:6322 / 6328
页数:7
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