Structure of an HIF-1α-pVHL Complex: Hydroxyproline Recognition in Signaling
摘要：
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.
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关键词：
Animals Humans Mice Macromolecular Substances Hydroxyproline Ligases Ubiquitin-Protein Ligases Transcription Factors Tumor Suppressor Proteins Crystallography, X-Ray
DOI：
10.1126/science.1073440
被引量：
年份：
2002
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