1LM8

Structure of a HIF-1a-pVHL-ElonginB-ElonginC Complex

Summary for 1LM8

• Entry DOI: 10.2210/pdb1lm8/pdb
• Descriptor: ELONGIN B, ELONGIN C, Von Hippel-Lindau disease tumor suppressor, ... (5 entities in total)
• Functional Keywords: regulation, tumor suppressor, oxygen sensing, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : Q15370 Q15369; Isoform 1: Cytoplasm. Isoform 3: Cytoplasm: P40337; Cytoplasm : Q16665
• Total number of polymer chains: 4
• Total formula weight: 44977.09

Authors

Min, J.-H.,Yang, H.,Ivan, M.,Gertler, F.,Kaelin JR., W.G.,Pavletich, N.P. (deposition date: 2002-04-30, release date: 2002-06-12, Last modification date: 2023-08-16)

Primary citation

Min, J.H.,Yang, H.,Ivan, M.,Gertler, F.,Kaelin Jr., W.G.,Pavletich, N.P.
Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.
Science, 296:1886-1889, 2002

PubMed 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.

PubMed: 12004076
DOI: 10.1126/science.1073440

Experimental method

X-RAY DIFFRACTION (1.85 Å)