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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5574
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pubmed:dateCreated |
2002-6-7
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyproline,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/VHL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Von Hippel-Lindau Tumor Suppressor...,
http://linkedlifedata.com/resource/pubmed/chemical/elongin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1095-9203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
7
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pubmed:volume |
296
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1886-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12004076-Amino Acid Sequence,
pubmed-meshheading:12004076-Animals,
pubmed-meshheading:12004076-Binding Sites,
pubmed-meshheading:12004076-Crystallography, X-Ray,
pubmed-meshheading:12004076-Humans,
pubmed-meshheading:12004076-Hydrogen Bonding,
pubmed-meshheading:12004076-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:12004076-Hydroxylation,
pubmed-meshheading:12004076-Hydroxyproline,
pubmed-meshheading:12004076-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:12004076-Ligases,
pubmed-meshheading:12004076-Macromolecular Substances,
pubmed-meshheading:12004076-Mice,
pubmed-meshheading:12004076-Models, Molecular,
pubmed-meshheading:12004076-Molecular Sequence Data,
pubmed-meshheading:12004076-Mutation,
pubmed-meshheading:12004076-Protein Conformation,
pubmed-meshheading:12004076-Protein Structure, Secondary,
pubmed-meshheading:12004076-Protein Structure, Tertiary,
pubmed-meshheading:12004076-Signal Transduction,
pubmed-meshheading:12004076-Transcription Factors,
pubmed-meshheading:12004076-Tumor Suppressor Proteins,
pubmed-meshheading:12004076-Ubiquitin-Protein Ligases,
pubmed-meshheading:12004076-Von Hippel-Lindau Tumor Suppressor Protein
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pubmed:year |
2002
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pubmed:articleTitle |
Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.
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pubmed:affiliation |
Cellular Biochemistry and Biophysics Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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