1lm8
From Proteopedia
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| , resolution 1.85Å | |||||||
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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
Page seeded by OCA on Thu Mar 20 12:32:28 2008
