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Titolo:
Molecular basis for Rac1 recognition by guanine nucleotide exchange factors
Autore:
Karnoub, AE; Worthylake, DK; Rossman, KL; Pruitt, WM; Campbell, SL; Sondek, J; Der, CJ;
Indirizzi:
Univ N Carolina, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 c Ctr, Chapel Hill, NC 27599 USA Univ N Carolina, Dept Pharmacol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 c Ctr, Chapel Hill, NC 27599 USA
Titolo Testata:
NATURE STRUCTURAL BIOLOGY
fascicolo: 12, volume: 8, anno: 2001,
pagine: 1037 - 1041
SICI:
1072-8368(200112)8:12<1037:MBFRRB>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
GTPASE-BINDING DOMAIN; DBL HOMOLOGY DOMAIN; RAS TRANSFORMATION; CRYSTAL-STRUCTURE; CDC42; PROTEIN; ACTIVATION; RHO; CYTOSKELETON; MUTAGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
23
Recensione:
Indirizzi per estratti:
Indirizzo: Der, CJ Univ N Carolina, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 hapel Hill, NC 27599 USA
Citazione:
A.E. Karnoub et al., "Molecular basis for Rac1 recognition by guanine nucleotide exchange factors", NAT ST BIOL, 8(12), 2001, pp. 1037-1041

Abstract

Rho GTPases are activated by a family of guanine nucleotide exchange factors (GEFs) known as DbI family proteins. The structural basis for how GEFs recognize and activate Rho GTPases is presently ill defined. Here, we utilized the crystal structure of the DH/PH domains of the Rac-specific GEF Tiam1in complex with Rac1 to determine the structural elements of Rac1 that regulate the specificity of this interaction. We show that residues in the Rac1 beta2-beta3 region are critical for Tiam1 recognition. Additionally, we determined that a single Rac1-to-Cdc42 mutation (W56F) was sufficient to abolish Rac1 sensitivity to Tiam1 and allow recognition by the Cdc42-specific DH/PH domains of Intersectin while not impairing Rac1 downstream activities. Oar findings identified unique GEF specificity determinants in Rac1 and provide important insights into the mechanism of DH/PH selection of GTPase targets.

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Documento generato il 05/04/20 alle ore 02:56:22