Structure of an HIF-1α-pVHL complex: Hydroxyproline recognition in signaling

Jung Hyun Min, Haifeng Yang, Mircea Ivan, Frank Gertler, William G. Kaelin, Nikola P. Pavietich

Research output: Contribution to journalArticle

500 Scopus citations

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-1α peptide-pVHL-ElonginB-ElonginC complex shows that HIF-1α binds to pVHL in an extended β 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 β sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling.

Original languageEnglish (US)
Pages (from-to)1886-1889
Number of pages4
JournalScience
Volume296
Issue number5574
DOIs
StatePublished - Jun 7 2002

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this

Min, J. H., Yang, H., Ivan, M., Gertler, F., Kaelin, W. G., & Pavietich, N. P. (2002). Structure of an HIF-1α-pVHL complex: Hydroxyproline recognition in signaling. Science, 296(5574), 1886-1889. https://doi.org/10.1126/science.1073440