1XD2

Crystal Structure of a ternary Ras:SOS:Ras*GDP complex

Summary for 1XD2

• Entry DOI: 10.2210/pdb1xd2/pdb
• Related: 1BKD 1NVU 1NVV 1NVW 1NVX 1XD4
• Descriptor: Transforming protein p21/H-Ras-1, Son of sevenless protein homolog 1, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: ras:sos complex, ras-nucleotide exchange factor complex, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side: P01112 P01112
• Total number of polymer chains: 3
• Total formula weight: 95293.68

Authors

Sondermann, H.,Soisson, S.M.,Boykevisch, S.,Yang, S.S.,Bar-Sagi, D.,Kuriyan, J. (deposition date: 2004-09-03, release date: 2004-11-02, Last modification date: 2023-08-23)

Primary citation

Sondermann, H.,Soisson, S.M.,Boykevisch, S.,Yang, S.S.,Bar-Sagi, D.,Kuriyan, J.
Structural analysis of autoinhibition in the ras activator son of sevenless.
Cell(Cambridge,Mass.), 119:393-405, 2004

PubMed Abstract: 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.

PubMed: 15507210
DOI: 10.1016/j.cell.2004.10.005

Experimental method

X-RAY DIFFRACTION (2.7 Å)