1faq: Difference between revisions
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|PDB= 1faq |SIZE=350|CAPTION= <scene name='initialview01'>1faq</scene> | |PDB= 1faq |SIZE=350|CAPTION= <scene name='initialview01'>1faq</scene> | ||
|SITE= <scene name='pdbsite=ZN1:Zn-Coordination+Residues'>ZN1</scene> and <scene name='pdbsite=ZN2:Zn-Coordination+Residues'>ZN2</scene> | |SITE= <scene name='pdbsite=ZN1:Zn-Coordination+Residues'>ZN1</scene> and <scene name='pdbsite=ZN2:Zn-Coordination+Residues'>ZN2</scene> | ||
|LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1far|1FAR]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1faq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1faq OCA], [http://www.ebi.ac.uk/pdbsum/1faq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1faq RCSB]</span> | |||
}} | }} | ||
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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 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. | 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== | ||
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[[Category: Campbell, S L.]] | [[Category: Campbell, S L.]] | ||
[[Category: Mott, H R.]] | [[Category: Mott, H R.]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
[[Category: phorbol-ester binding]] | [[Category: phorbol-ester binding]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:19:13 2008'' | ||
Revision as of 20:19, 30 March 2008
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| Sites: | and | ||||||
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| Related: | 1FAR
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
RAF-1 CYSTEINE RICH DOMAIN, NMR, 27 STRUCTURES
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
1FAQ is a Single protein structure of sequence from Homo sapiens. 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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