Structure of an HIF-1α-pVHL complex: Hydroxyproline recognition in signaling Journal Article
| Authors: | Min, J. H.; Yang, H.; Ivan, M.; Gertler, F.; Kaelin, W. G. Jr; Pavletich, N. P. |
| Article Title: | Structure of an HIF-1α-pVHL complex: Hydroxyproline recognition in signaling |
| 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. |
| Keywords: | signal transduction; genetics; mutation; molecular genetics; protein conformation; proteins; mouse; animal; metabolism; animals; mice; signaling; ubiquitin protein ligase; oxygen; protein binding; transcription factor; oncology; physiology; carcinogenesis; transcription factors; chemistry; amino acid sequence; molecular sequence data; molecular recognition; tumor suppressor proteins; binding site; hydrogen bond; hydrogen bonding; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; chemical structure; molecular structure; conformation; von hippel lindau disease; protein secondary structure; x ray crystallography; tumor suppressor protein; biochemistry; hypoxia inducible factor 1alpha; ubiquitin-protein ligases; protein tertiary structure; protein structure, secondary; von hippel lindau protein; hif1a protein, human; hypoxia-inducible factor 1, alpha subunit; macromolecule; macromolecular substances; proline; ligase; mutations; ligases; cells; hypoxia inducible factor 1; hydroxylation; hydrophobicity; beta sheet; vhl protein, human; von hippel-lindau tumor suppressor protein; cancer; humans; human; priority journal; article; hydroxyproline; elongin |
| Journal Title: | Science |
| Volume: | 296 |
| Issue: | 5574 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2002-06-07 |
| Start Page: | 1886 |
| End Page: | 1889 |
| Language: | English |
| DOI: | 10.1126/science.1073440 |
| PUBMED: | 12004076 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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