PDBsum entry 1foe

Signaling protein, immune system/signali

PDB id: 1foe

Contents

Protein chains

368 a.a. *

177 a.a. *

Ligands

SO4 ×4

Waters ×93

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structure of rac1 in complex with the guanine nucleotide exchange region of tiam1.

Authors

D.K.Worthylake, K.L.Rossman, J.Sondek.

Ref.

Nature, 2000, 408, 682-688. [DOI no: 10.1038/35047014]

PubMed id

11130063

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.

Figure 2.
Figure 2: Structural comparison of the Tiam1/Rac1 complex with the Sos1 DH/PH domains. a, The Tiam1/Rac1 complex. Switch regions of Rac1 are red; the rest of the G protein is green. Tiam1 DH and PH domains are yellow and blue, respectively; disordered regions are orange; and black dashed line highlights 9 and its equivalent in Sos1 (c). b, View in a rotated 90° about the horizontal. c, Structure of the Sos1 DH (yellow) and PH (blue) domains15 aligned with Tiam1 orientated as in a by least squares superposition of the 72 -carbon atoms of CR1-CR3 (r.m.s. deviations, 1.52 Å). Yellow dashed line indicates disordered residues in the Sos1 DH domain. d, View in c rotated 90° about the horizontal. Note, position of the Sos1 PH domain overlaps the G-protein-binding interface. Figures 2, 5 and 6c were made using MOLSCRIPT40 and Raster3D^41.

Figure 3.
Figure 3: Representation of Tiam1/Rac1 interface contacts. The model of Rac1 on the left in green (with switch regions in red) has been rotated 180° about the vertical axis from its relative orientation with respect to the DH domain (on right in yellow) to display the two interface surfaces. Residues in black type lose >10 Å2 of accessible surface area on complex formation. Associated intermolecular contacts are listed below, colour coded by interaction type (red, van der Waal's; green, hydrogen bonds; blue, ionic) and starred if non-ionic but involving side-chain atoms. Figure was made using Ribbons42.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2000, 408, 682-688) copyright 2000.