Letter | Published:

Structural basis for the interaction of Ras with RaIGDS

Nature Structural Biology volume 5, pages 422426 (1998) | Download Citation

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Abstract

The Ras protein signals to a number of distinct pathways by interacting with diverse downstream effectors. Among the effectors of Ras are the Raf kinase and RalGDS, a guanine nucleotide dissociation stimulator specific for Ral. Despite the absence of significant sequence similarities, both effectors bind directly to Ras, but with different specificities. We report here the 2.1 Å crystal structure of the complex between Ras and the Ras-interacting domain (RID) of RalGDS. This structure reveals that the β-sheet of the RID joins the switch I region of Ras to form an extended β-sheet with a topology similar to that found in the Rap–Raf complex. However, the side chain interactions at the joining junctions of the two interacting systems and the relative orientation of the two binding domains are distinctly different. Furthermore, in the case of the Ras–RID complex a second RID molecule also interacts with a different part of the Ras molecule, the switch II region. These findings account for the cross-talk between the Ras and Ral pathways and the specificity with which Ras distinguishes the two effectors.

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Author information

Affiliations

  1. Department of Chemistry and E. O. Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA.

    • Lan Huang
    •  & Sung-Hou Kim
  2. Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.

    • Franz Hofer
    •  & G. Steven Martin

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Correspondence to Sung-Hou Kim.

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DOI

https://doi.org/10.1038/nsb0698-422

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