Structural and biochemical analysis of Ras‐effector signaling via RalGDS

FEBS Letters - Tập 451 Số 2 - Trang 175-180 - 1999
Ingrid R. Vetter1, Thomas Linnemann1, Sabine Wohlgemuth1, Matthias Geyer2, Hans Robert Kalbitzer2, Christian Herrmann1, A. Wittinghofer1
1Max-Planck-Institut für molekulare Physiologie, Abteilung Strukturelle Biologie, Rheinlanddamm 201, D-44139 Dortmund, Germany
2Institut für Biophysik und Physikalische Biochemie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany

Tóm tắt

The structure of the complex of Ras with the Ras‐binding domain of its effector RalGDS (RGS‐RBD), the first genuine Ras‐effector complex, has been solved by X‐ray crystallography. As with the Rap‐RafRBD complex (Nasser et al., 1995), the interaction is via an inter‐protein β‐sheet between the switch I region of Ras and the second strand of the RGS‐RBD sheet, but the details of the interactions in the interface are remarkably different. Mutational studies were performed to investigate the contribution of selected interface residues to the binding affinity. Gel filtration experiments show that the Ras·RGS‐RBD complex is a monomer. The results are compared to a recently determined structure of a similar complex using a Ras mutant (Huang et al., 1998) and are discussed in relation to partial loss‐of‐function mutations and the specificity of Ras versus Rap binding.

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