1far: Difference between revisions
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==Overview== | ==Overview== | ||
The Raf-1 protein kinase is the best-characterized downstream effector of, activated Ras. Interaction with Ras leads to Raf-1 activation and results, in transduction of cell growth and differentiation signals. The details of, Raf-1 activation are unclear, but our characterization of a second, Ras-binding site in the cysteine-rich domain (CRD) and the involvement of, both Ras-binding sites in effective Raf-1-mediated transformation provides, insight into the molecular aspects and consequences of Ras-Raf, interactions. The Raf-1 CRD is a member of an emerging family of domains, many of which are found within signal transducing proteins. Several, contain binding sites for diacylglycerol (or phorbol esters) and, phosphatidylserine and are believed to play a role in membrane, translocation and ... | The Raf-1 protein kinase is the best-characterized downstream effector of, activated Ras. Interaction with Ras leads to Raf-1 activation and results, in transduction of cell growth and differentiation signals. The details of, Raf-1 activation are unclear, but our characterization of a second, Ras-binding site in the cysteine-rich domain (CRD) and the involvement of, both Ras-binding sites in effective Raf-1-mediated transformation provides, insight into the molecular aspects and consequences of Ras-Raf, interactions. The Raf-1 CRD is a member of an emerging family of domains, many of which are found within signal transducing proteins. Several, contain binding sites for diacylglycerol (or phorbol esters) and, phosphatidylserine and are believed to play a role in membrane, translocation and enzyme activation. The CRD from Raf-1 does not bind, diacylglycerol but interacts with Ras and phosphatidylserine. To, investigate the ligand-binding specificities associated with CRDs, we have, determined the solution structure of the Raf-1 CRD using heteronuclear, multidimensional NMR. We show that there are differences between this, structure and the structures of two related domains from protein kinase C, (PKC). The differences are confined to regions of the CRDs involved in, binding phorbol ester in the PKC domains. Since phosphatidylserine is a, common ligand, we expect its binding site to be located in regions where, the structures of the Raf-1 and PKC domains are similar. The structure of, the Raf-1 CRD represents an example of this family of domains that does, not bind diacylglycerol and provides a framework for investigating its, interactions with other molecules. | ||
==About this Structure== | ==About this Structure== | ||
1FAR is a | 1FAR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Sites: ZN1 and ZN2. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FAR OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
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Revision as of 14:36, 5 November 2007
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RAF-1 CYSTEINE RICH DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE
OverviewOverview
The Raf-1 protein kinase is the best-characterized downstream effector of, activated Ras. Interaction with Ras leads to Raf-1 activation and results, in transduction of cell growth and differentiation signals. The details of, Raf-1 activation are unclear, but our characterization of a second, Ras-binding site in the cysteine-rich domain (CRD) and the involvement of, both Ras-binding sites in effective Raf-1-mediated transformation provides, insight into the molecular aspects and consequences of Ras-Raf, interactions. The Raf-1 CRD is a member of an emerging family of domains, many of which are found within signal transducing proteins. Several, contain binding sites for diacylglycerol (or phorbol esters) and, phosphatidylserine and are believed to play a role in membrane, translocation and enzyme activation. The CRD from Raf-1 does not bind, diacylglycerol but interacts with Ras and phosphatidylserine. To, investigate the ligand-binding specificities associated with CRDs, we have, determined the solution structure of the Raf-1 CRD using heteronuclear, multidimensional NMR. We show that there are differences between this, structure and the structures of two related domains from protein kinase C, (PKC). The differences are confined to regions of the CRDs involved in, binding phorbol ester in the PKC domains. Since phosphatidylserine is a, common ligand, we expect its binding site to be located in regions where, the structures of the Raf-1 and PKC domains are similar. The structure of, the Raf-1 CRD represents an example of this family of domains that does, not bind diacylglycerol and provides a framework for investigating its, interactions with other molecules.
About this StructureAbout this Structure
1FAR is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Structure known Active Sites: ZN1 and ZN2. Full crystallographic information is available from OCA.
ReferenceReference
The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site., Mott HR, Carpenter JW, Zhong S, Ghosh S, Bell RM, Campbell SL, Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8312-7. PMID:8710867
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