title: Catalytic competence of the Ras-GEF domain of hSos1 requires intra-REM domain interactions mediated by phenylalanine 577.
abstract: 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.
authors.affiliation: Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sacco
authors.forename: David
authors.initials: D
authors.lastname: Metalli
authors.forename: Stefano
authors.initials: S
authors.lastname: Busti
authors.forename: Sonia
authors.initials: S
authors.lastname: Fantinato
authors.forename: Annalisa
authors.initials: A
authors.lastname: D'Urzo
authors.forename: Valeria
authors.initials: V
authors.lastname: Mapelli
authors.forename: Lilia
authors.initials: L
authors.lastname: Alberghina
authors.forename: Marco
authors.initials: M
authors.lastname: Vanoni
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D001665:Binding Sites; D006801:Humans; D010649:Phenylalanine / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D020837:SOS1 Protein / Q000737:chemistry* / Q000235:genetics
chemical_list: D020837:SOS1 Protein; D010649:Phenylalanine