Scheffzek, K., Grunewald, P., Wohlgemuth, S., Kabsch, W., Tu, H., Wigler, M. H., Wittinghofer, A., Herrmann, C. (November 2001) The Ras-Byr2RBD complex: Structural basis for Ras effector recognition in yeast. Structure, 9 (11). pp. 1043-1050. ISSN 0969-2126
Abstract
Background-The small GTP binding protein Ras has important roles in cellular growth and differentiation. Mutant Ras is permanently active and contributes to cancer development. In its activated form, Ras interacts with effector proteins, frequently initiating a kinase cascade. In the lower eukaryotic Schizosaccharomyces pombe, Byr2 kinase represents a Ras target that In terms of signal-transduction hierarchy can be considered a homolog of mammalian Raf-kinase. The activation mechanism of protein kinases by Ras is not understood, and there is no detailed structural information about Ras binding domains (RBDs) in nonmammalian organisms. Results: The crystal structure of the Ras-Byr2RBD complex at 3 Angstrom resolution shows a complex architecture similar to that observed in mammalian homologous systems, with an interprotein beta sheet stabilized by predominantly polar interactions between the interacting components. The C-terminal half of the Ras switch I region contains most of the contact anchors, while on the Byr2 side, a number of residues from topologically distinct regions are Involved in complex stabilization. A C-terminal helical segment, which is not present in the known mammalian homologous systems and which is part of the auto-inhibitory region, has an additional binding site outside the switch I region. Conclusions: The structure of the Ras-Byr2 complex confirms the Ras binding module as a communication element mediating Ras-effector interactions; the Ras-Byr2 complex is also conserved in a lower eukaryotic system like yeast, which is in contrast to other small GTPase families. The extra helical segment might be involved in kinase activation.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Byr2-kinase mutational analysis Schizosaccharomyces pombe Ras signaling GTP binding protein, cancer GTPase X-ray crystallography WISKOTT-ALDRICH-SYNDROME Wiskott Aldrich syndrome GUANINE-NUCLEOTIDE EXCHANGE Guanine nucleotide exchange GTPASE-BINDING GTPase binding domain DOMAIN PROTEIN-KINASE protein kinase SCHIZOSACCHAROMYCES-POMBE Schizosaccharomyces pombe Pombe DISSOCIATION dissociation STIMULATOR stimulator SIGNAL-TRANSDUCTION signal transduction CRYSTAL-STRUCTURE crystal structure RHO-KINASE RHO kinase H-RAS |
| Subjects: | diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene organism description > yeast |
| CSHL Authors: | |
| Communities: | CSHL labs > Wigler lab |
| Depositing User: | CSHL Librarian |
| Date: | November 2001 |
| Date Deposited: | 05 Apr 2012 17:06 |
| Last Modified: | 02 Nov 2016 16:53 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/26013 |
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