1lm8
From Proteopedia
(New page: 200px<br /> <applet load="1lm8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lm8, resolution 1.85Å" /> '''Structure of a HIF-...) |
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| - | [[Image:1lm8.gif|left|200px]]<br /> | + | [[Image:1lm8.gif|left|200px]]<br /><applet load="1lm8" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1lm8" size=" | + | |
caption="1lm8, resolution 1.85Å" /> | caption="1lm8, resolution 1.85Å" /> | ||
'''Structure of a HIF-1a-pVHL-ElonginB-ElonginC Complex'''<br /> | '''Structure of a HIF-1a-pVHL-ElonginB-ElonginC Complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The ubiquitination of the hypoxia-inducible factor (HIF) by the von | + | The ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) plays a central role in the cellular response to changes in oxygen availability. pVHL binds to HIF only when a conserved proline in HIF is hydroxylated, a modification that is oxygen-dependent. The 1.85 angstrom structure of a 20-residue HIF-1alpha peptide-pVHL-ElonginB-ElonginC complex shows that HIF-1alpha binds to pVHL in an extended beta strand-like conformation. The hydroxyproline inserts into a gap in the pVHL hydrophobic core, at a site that is a hotspot for tumorigenic mutations, with its 4-hydroxyl group recognized by buried serine and histidine residues. Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1LM8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1LM8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LM8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Gertler, F.]] | [[Category: Gertler, F.]] | ||
[[Category: Ivan, M.]] | [[Category: Ivan, M.]] | ||
| - | [[Category: JR., W | + | [[Category: JR., W G.Kaelin.]] |
[[Category: Min, J-H]] | [[Category: Min, J-H]] | ||
| - | [[Category: Pavletich, N | + | [[Category: Pavletich, N P.]] |
[[Category: Yang, H.]] | [[Category: Yang, H.]] | ||
[[Category: oxygen sensing]] | [[Category: oxygen sensing]] | ||
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[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:46:15 2008'' |
Revision as of 11:46, 21 February 2008
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Structure of a HIF-1a-pVHL-ElonginB-ElonginC Complex
Contents |
Overview
The ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) plays a central role in the cellular response to changes in oxygen availability. pVHL binds to HIF only when a conserved proline in HIF is hydroxylated, a modification that is oxygen-dependent. The 1.85 angstrom structure of a 20-residue HIF-1alpha peptide-pVHL-ElonginB-ElonginC complex shows that HIF-1alpha binds to pVHL in an extended beta strand-like conformation. The hydroxyproline inserts into a gap in the pVHL hydrophobic core, at a site that is a hotspot for tumorigenic mutations, with its 4-hydroxyl group recognized by buried serine and histidine residues. Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling.
Disease
Known diseases associated with this structure: Hemangioblastoma, cerebellar, somatic OMIM:[608537], Pheochromocytoma OMIM:[608537], Polycythemia, benign familial OMIM:[608537], Renal cell carcinoma, somatic OMIM:[608537], von Hippel-Lindau syndrome OMIM:[608537]
About this Structure
1LM8 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling., Min JH, Yang H, Ivan M, Gertler F, Kaelin WG Jr, Pavletich NP, Science. 2002 Jun 7;296(5574):1886-9. Epub 2002 May 9. PMID:12004076
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