1xd2
From Proteopedia
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| , resolution 2.70Å | |||||||
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| Ligands: | , and | ||||||
| Gene: | HRAS, HRAS1 (Homo sapiens), SOS1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of a ternary Ras:SOS:Ras*GDP complex
Contents |
Overview
The classical model for the activation of the nucleotide exchange factor Son of sevenless (SOS) involves its recruitment to the membrane, where it engages Ras. The recent discovery that Ras*GTP is an allosteric activator of SOS indicated that the regulation of SOS is more complex than originally envisaged. We now present crystallographic and biochemical analyses of a construct of SOS that contains the Dbl homology-pleckstrin homology (DH-PH) and catalytic domains and show that the DH-PH unit blocks the allosteric binding site for Ras and suppresses the activity of SOS. SOS is dependent on Ras binding to the allosteric site for both a lower level of activity, which is a result of Ras*GDP binding, and maximal activity, which requires Ras*GTP. The action of the DH-PH unit gates a reciprocal interaction between Ras and SOS, in which Ras converts SOS from low to high activity forms as Ras*GDP is converted to Ras*GTP by SOS.
Disease
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 Structure
1XD2 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural analysis of autoinhibition in the Ras activator Son of sevenless., Sondermann H, Soisson SM, Boykevisch S, Yang SS, Bar-Sagi D, Kuriyan J, Cell. 2004 Oct 29;119(3):393-405. PMID:15507210
Page seeded by OCA on Sun Mar 23 14:12:18 2008
