PDBsum entry 1bkd

Complex(oncogene protein/exchange factor

PDB id: 1bkd

Contents

Protein chains

166 a.a. *

439 a.a. *

Waters ×26

* Residue conservation analysis

References listed in PDB file

Key reference

Title

The structural basis of the activation of ras by sos.

Authors

P.A.Boriack-Sjodin, S.M.Margarit, D.Bar-Sagi, J.Kuriyan.

Ref.

Nature, 1998, 394, 337-343. [DOI no: 10.1038/28548]

PubMed id

9690470

Abstract

The crystal structure of human H-Ras complexed with the Ras guanine-nucleotide-exchange-factor region of the Son of sevenless (Sos) protein has been determined at 2.8 A resolution. The normally tight interaction of nucleotides with Ras is disrupted by Sos in two ways. First, the insertion into Ras of an alpha-helix from Sos results in the displacement of the Switch 1 region of Ras, opening up the nucleotide-binding site. Second, side chains presented by this helix and by a distorted conformation of the Switch 2 region of Ras alter the chemical environment of the binding site for the phosphate groups of the nucleotide and the associated magnesium ion, so that their binding is no longer favoured. Sos does not impede the binding sites for the base and the ribose of GTP or GDP, so the Ras-Sos complex adopts a structure that allows nucleotide release and rebinding.

Figure 2.
Figure 2 The complex of human H-Ras with the exchange-factor region of human Sos1. a, The N-domain of Sos (residues 568-741) is shown blue; the catalytic domain (residues 752-1044) is green; the Switch 1 and Switch 2 segments and the P-loop region of Ras (as defined here) are orange and red, respectively; conserved regions (SCRs) among Ras-family exchange factors are cyan2,17. Disordered residues of Sos are shown as dotted lines. This and all other ribbon diagrams were generated using RIBBONS44. b, The Ras-Sos complex is shown with the catalytic domain of Sos depicted as a molecular surface. Conserved residues Ile 956 and Phe 958 in the catalytic domain that form a hydrophobic interface with the N-domain are labelled. This and all other figures with molecular surfaces were generated using GRASP45.

Figure 3.
Figure 3 Interface surfaces of the Ras-Sos complex. a, Residues of Ras that form direct interactions with Sos are shown as red spheres; additional residues at the interface are orange spheres. The nucleotide is shown for reference only and is not present in the structure. b, The interface surface of Ras; the orientation is the same as in a. The surface is coloured using a gradient: bright orange indicates atoms <4 ? from Sos, white indicates atoms >7 ? from Sos, lighter shades of orange indicate intermediate distances. Sos (N-domain deleted) is shown as a green ribbon. c, The primary sequence of Ras.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1998, 394, 337-343) copyright 1998.