1kbe
From Proteopedia
(New page: 200px<br /><applet load="1kbe" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kbe" /> '''Solution structure of the cysteine-rich C1 d...) |
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| - | [[Image:1kbe.jpg|left|200px]]<br /><applet load="1kbe" size=" | + | [[Image:1kbe.jpg|left|200px]]<br /><applet load="1kbe" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1kbe" /> | caption="1kbe" /> | ||
'''Solution structure of the cysteine-rich C1 domain of Kinase Suppressor of Ras'''<br /> | '''Solution structure of the cysteine-rich C1 domain of Kinase Suppressor of Ras'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway | + | Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway that acts as a molecular scaffold to promote signal transmission from Raf-1 to MEK and MAPK. All KSR proteins contain a conserved cysteine-rich C1 domain, and studies have implicated this domain in the regulation of KSR1 subcellular localization and function. To further elucidate the biological role of the KSR1 C1 domain, we have determined its three-dimensional solution structure using nuclear magnetic resonance (NMR). We find that while the overall topology of the KSR1 C1 domain is similar to the C1 domains of Raf-1 and PKCgamma, the predicted ligand-binding region and the surface charge distribution are unique. Moreover, by generating chimeric proteins in which these domains have been swapped, we find that the C1 domains of Raf-1, PKCgamma, and KSR1 are not functionally interchangeable. The KSR1 C1 domain does not bind with high affinity or respond biologically to phorbol esters or ceramide, and it does not interact directly with Ras, indicating that the putative ligand(s) for the KSR1 C1 domain are distinct from those that interact with PKCgamma and Raf-1. In addition, our analysis of the chimeric proteins supports the model that Raf-1 is a ceramide-activated kinase and that its C1 domain is involved in the ceramide-mediated response. Finally, our findings demonstrate an absolute requirement of the KSR1 C1 domain in mediating the membrane localization of KSR1, a crucial feature of its scaffolding activity. Together, these results underscore the functional specificity of these important regulatory domains and demonstrate that the structural features of the C1 domains can provide valuable insight into their ligand-binding properties. |
==About this Structure== | ==About this Structure== | ||
| - | 1KBE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1KBE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KBE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Byrd, R | + | [[Category: Byrd, R A.]] |
| - | [[Category: Horita, D | + | [[Category: Horita, D A.]] |
| - | [[Category: Morrison, D | + | [[Category: Morrison, D K.]] |
| - | [[Category: Waugh, D | + | [[Category: Waugh, D S.]] |
[[Category: Zhou, M.]] | [[Category: Zhou, M.]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: zinc-binding protein]] | [[Category: zinc-binding protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:32:10 2008'' |
Revision as of 11:32, 21 February 2008
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Solution structure of the cysteine-rich C1 domain of Kinase Suppressor of Ras
Overview
Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway that acts as a molecular scaffold to promote signal transmission from Raf-1 to MEK and MAPK. All KSR proteins contain a conserved cysteine-rich C1 domain, and studies have implicated this domain in the regulation of KSR1 subcellular localization and function. To further elucidate the biological role of the KSR1 C1 domain, we have determined its three-dimensional solution structure using nuclear magnetic resonance (NMR). We find that while the overall topology of the KSR1 C1 domain is similar to the C1 domains of Raf-1 and PKCgamma, the predicted ligand-binding region and the surface charge distribution are unique. Moreover, by generating chimeric proteins in which these domains have been swapped, we find that the C1 domains of Raf-1, PKCgamma, and KSR1 are not functionally interchangeable. The KSR1 C1 domain does not bind with high affinity or respond biologically to phorbol esters or ceramide, and it does not interact directly with Ras, indicating that the putative ligand(s) for the KSR1 C1 domain are distinct from those that interact with PKCgamma and Raf-1. In addition, our analysis of the chimeric proteins supports the model that Raf-1 is a ceramide-activated kinase and that its C1 domain is involved in the ceramide-mediated response. Finally, our findings demonstrate an absolute requirement of the KSR1 C1 domain in mediating the membrane localization of KSR1, a crucial feature of its scaffolding activity. Together, these results underscore the functional specificity of these important regulatory domains and demonstrate that the structural features of the C1 domains can provide valuable insight into their ligand-binding properties.
About this Structure
1KBE is a Single protein structure of sequence from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR)., Zhou M, Horita DA, Waugh DS, Byrd RA, Morrison DK, J Mol Biol. 2002 Jan 18;315(3):435-46. PMID:11786023
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