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- Title
Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.
- Authors
Min, Jung-Hyun; Yang, Haifeng; Ivan, Mircea; Gertler, Frank; Kaelin, William G, Jr; Pavletich, Nikola P
- Abstract
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.
- Publication
Science (New York, N.Y.), 2002, Vol 296, Issue 5574, p1886
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1073440