The allosteric Ras-binding site (green) of SOS is blocked by its own domains (gray and olive).

KURIYAN/ELSEVIER

A Ras activator takes care with its own inhibitory domain to prevent an accidental Ras outbreak, according to structural studies from Holger Sondermann, John Kuriyan (University of California, Berkeley, CA), and colleagues.

Ras turns on MAPK pathways that trigger big changes in cell physiology that lead to cell growth, survival, or differentiation. “Its pathways control so many [extensive] outputs, you really want to avoid false activation,” says Sondermann. His work now shows that the necessary care is taken by Ras's nucleotide exchange factor, SOS.

SOS helps Ras expel GDP to make room for GTP, which activates Ras. RasGTP then begins a positive feedback loop—previous studies show that RasGTP binds to an allosteric site on SOS and stimulates its exchange activity. But the new structures, which include a larger...

The Rockefeller University Press
2004
The Rockefeller University Press
2004
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