The structural basis of the activation of Ras by Sos

The crystal structure of human H-Ras complexed with the pas guanine-nucleotide-exchange-factor region of the Son of sevenless (Sos) protein has been determined at 2.8 Angstrom resolution. The normally tight interaction of nucleotides with pas is disrupted by Sos in two ways. First, the insertion into gas 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 pas alter title 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 sop, so the Ras-Sos complex adopts a structure that allows nucleotide release and rebinding.