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Catalytic competence of the Ras–GEF domain of hSos1 requires intra‐REM domain interactions mediated by Phenylalanine 577
Author(s) -
Sacco Elena,
Metalli David,
Busti Stefano,
Fantinato Sonia,
D'Urzo Annalisa,
Mapelli Valeria,
Alberghina Lilia,
Vai Marco
Publication year - 2006
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/j.febslet.2006.10.040
Subject(s) - guanine nucleotide exchange factor , phenylalanine , chemistry , in vivo , guanine , biophysics , domain (mathematical analysis) , catalysis , in vitro , biochemistry , nucleotide , microbiology and biotechnology , stereochemistry , biology , gtpase , genetics , amino acid , gene , mathematical analysis , mathematics
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.