
Structural Analysis of Autoinhibition in the Ras Activator Son of Sevenless
Holger Sondermann*, Stephen M. Soisson*, Sean Boykevisch, Shao-Song Yang,
Dafna Bar-Sagi, and John Kuriyan
Cell. 2004 Oct 29;119(3):393-405.
Link to Cell Press
*These authors contributed equally to this work.
Abstract / Figures from the
paper
/ PDB coordinates
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- and 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.
Illustrations from the paper. Click on the
small image to get a bigger one.




PDB Coordinates
PDB code 1XD2
PDB code 1XD4
PDB code 1XDV