1NVU

Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS

Summary for 1NVU

• Entry DOI: 10.2210/pdb1nvu/pdb
• Related: 1BDK 1NVV 1NVW 1NVX
• Descriptor: Transforming protein p21/H-RAS-1, Son of sevenless protein homolog 1, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: proto-oncogene, gtp binding, guanine nucleotide release factor, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side: P01112
• Total number of polymer chains: 3
• Total formula weight: 95277.40

Authors

Margarit, S.M.,Sondermann, H.,Hall, B.E.,Nagar, B.,Hoelz, A.,Pirruccello, M.,Bar-Sagi, D.,Kuriyan, J. (deposition date: 2003-02-04, release date: 2003-04-01, Last modification date: 2023-08-16)

Primary citation

Margarit, S.M.,Sondermann, H.,Hall, B.E.,Nagar, B.,Hoelz, A.,Pirruccello, M.,Bar-Sagi, D.,Kuriyan, J.
Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS
Cell(Cambridge,Mass.), 112:685-695, 2003

PubMed Abstract: Growth factor receptors activate Ras by recruiting the nucleotide exchange factor son of sevenless (SOS) to the cell membrane, thereby triggering the production of GTP-loaded Ras. Crystallographic analyses of Ras bound to the catalytic module of SOS have led to the unexpected discovery of a highly conserved Ras binding site on SOS that is located distal to the active site and is specific for Ras.GTP. The crystal structures suggest that Ras.GTP stabilizes the active site of SOS allosterically, and we show that Ras.GTP forms ternary complexes with SOS(cat) in solution and increases significantly the rate of SOS(cat)-stimulated nucleotide release from Ras. These results demonstrate the existence of a positive feedback mechanism for the spatial and temporal regulation of Ras.

PubMed: 12628188
DOI: 10.1016/S0092-8674(03)00149-1

Experimental method

X-RAY DIFFRACTION (2.2 Å)