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

474 Citations (Scopus)

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
Externally publishedYes

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Hypoxia-Inducible Factor 1
Hydroxyproline
Oxygen
Ubiquitination
Histidine
Proline
Hydroxyl Radical
Serine
Peptides
Mutation
Hypoxia
Neoplasms

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

Structure of an HIF-1α-pVHL complex : Hydroxyproline recognition in signaling. / Min, Jung Hyun; Yang, Haifeng; Ivan, Mircea; Gertler, Frank; Kaelin, William G.; Pavietich, Nikola P.

In: Science, Vol. 296, No. 5574, 07.06.2002, p. 1886-1889.

Research output: Contribution to journalArticle

Min, JH, Yang, H, Ivan, M, Gertler, F, Kaelin, WG & Pavietich, NP 2002, 'Structure of an HIF-1α-pVHL complex: Hydroxyproline recognition in signaling', Science, vol. 296, no. 5574, pp. 1886-1889. https://doi.org/10.1126/science.1073440
Min JH, Yang H, Ivan M, Gertler F, Kaelin WG, Pavietich NP. Structure of an HIF-1α-pVHL complex: Hydroxyproline recognition in signaling. Science. 2002 Jun 7;296(5574):1886-1889. https://doi.org/10.1126/science.1073440
Min, Jung Hyun ; Yang, Haifeng ; Ivan, Mircea ; Gertler, Frank ; Kaelin, William G. ; Pavietich, Nikola P. / Structure of an HIF-1α-pVHL complex : Hydroxyproline recognition in signaling. In: Science. 2002 ; Vol. 296, No. 5574. pp. 1886-1889.
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