1k8r
From Proteopedia
(New page: 200px<br /> <applet load="1k8r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1k8r, resolution 3.Å" /> '''Crystal structure of ...) |
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caption="1k8r, resolution 3.Å" /> | caption="1k8r, resolution 3.Å" /> | ||
'''Crystal structure of Ras-Bry2RBD complex'''<br /> | '''Crystal structure of Ras-Bry2RBD complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: The small GTP binding protein Ras has important roles in | + | 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 A 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1K8R is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Schizosaccharomyces_pombe Schizosaccharomyces pombe] with MG and GNP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1K8R is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Schizosaccharomyces_pombe Schizosaccharomyces pombe] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GNP:'>GNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K8R OCA]. |
==Reference== | ==Reference== | ||
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[[Category: ubiquitin fold]] | [[Category: ubiquitin fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:31:21 2008'' |
Revision as of 11:31, 21 February 2008
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Crystal structure of Ras-Bry2RBD complex
Contents |
Overview
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 A 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.
Disease
Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Thyroid carcinoma, follicular, somatic OMIM:[190020]
About this Structure
1K8R is a Protein complex structure of sequences from Homo sapiens and Schizosaccharomyces pombe with and as ligands. Full crystallographic information is available from OCA.
Reference
The Ras-Byr2RBD complex: structural basis for Ras effector recognition in yeast., Scheffzek K, Grunewald P, Wohlgemuth S, Kabsch W, Tu H, Wigler M, Wittinghofer A, Herrmann C, Structure. 2001 Nov;9(11):1043-50. PMID:11709168
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