1FOE

CRYSTAL STRUCTURE OF RAC1 IN COMPLEX WITH THE GUANINE NUCLEOTIDE EXCHANGE REGION OF TIAM1

Summary for 1FOE

• Entry DOI: 10.2210/pdb1foe/pdb
• NMR Information: BMRB: 5511
• Descriptor: T-LYMPHOMA INVASION AND METASTASIS INDUCING PROTEIN 1, RAS-RELATED C3 BOTULINUM TOXIN SUBSTRATE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: dbl homology domain, pleckstrin homology domain, gtpase, guanine nucleotide exchange factor, signaling protein, immune system-signaling protein complex, immune system/signaling protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cell junction (By similarity): Q60610; Cell membrane; Lipid-anchor; Cytoplasmic side (By similarity): P63000
• Total number of polymer chains: 8
• Total formula weight: 254537.46

Authors

Worthylake, D.K.,Rossman, K.L.,Sondek, J. (deposition date: 2000-08-27, release date: 2001-01-17, Last modification date: 2011-07-13)

Primary citation

Worthylake, D.K.,Rossman, K.L.,Sondek, J.
Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1.
Nature, 408:682-688, 2000

PubMed Abstract: The principal guanine nucleotide exchange factors for Rho family G proteins contain tandem Dbl-homology (DH) and pleckstrin-homology (PH) domains that catalyse nucleotide exchange and the activation of G proteins. Here we have determined the crystal structure of the DH and PH domains of the T-lymphoma invasion and metastasis factor 1 (Tiam1) protein in complex with its cognate Rho family G protein, Rac1. The two switch regions of Rac1 are stabilized in conformations that disrupt both magnesium binding and guanine nucleotide interaction. The resulting cleft in Rac1 is devoid of nucleotide and highly exposed to solvent. The PH domain of Tiam1 does not contact Rac1, and the position and orientation of the PH domain is markedly altered relative to the structure of the uncomplexed, GTPase-free DH/PH element from Sos1. The Tiam1/Rac1 structure highlights the interactions that catalyse nucleotide exchange on Rho family G proteins, and illustrates structural determinants dictating specificity between individual Rho family members and their associated Dbl-related guanine nucleotide exchange factors.

PubMed: 11130063
DOI: 10.1038/35047014

Experimental method

X-RAY DIFFRACTION (2.8 Å)