1nvw
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| , resolution 2.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | HRAS OR HRAS1 (Homo sapiens), SOS1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural evidence for feedback activation by RasGTP of the Ras-specific nucleotide exchange factor SOS
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Fibromatosis, gingival OMIM:[182530], Noonan syndrome 4 OMIM:[182530], Thyroid carcinoma, follicular, somatic OMIM:[190020]
About this StructureAbout this Structure
1NVW is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS., Margarit SM, Sondermann H, Hall BE, Nagar B, Hoelz A, Pirruccello M, Bar-Sagi D, Kuriyan J, Cell. 2003 Mar 7;112(5):685-95. PMID:12628188
Page seeded by OCA on Thu Mar 20 13:02:23 2008