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1lm8
From Proteopedia
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|PDB= 1lm8 |SIZE=350|CAPTION= <scene name='initialview01'>1lm8</scene>, resolution 1.85Å | |PDB= 1lm8 |SIZE=350|CAPTION= <scene name='initialview01'>1lm8</scene>, resolution 1.85Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lm8 OCA], [http://www.ebi.ac.uk/pdbsum/1lm8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lm8 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Hemangioblastoma, cerebellar, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]], Pheochromocytoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]], Polycythemia, benign familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]], Renal cell carcinoma, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]], von Hippel-Lindau syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608537 608537]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:04:37 2008'' |
Revision as of 19:04, 30 March 2008
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| , resolution 1.85Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of a HIF-1a-pVHL-ElonginB-ElonginC Complex
Overview
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.
About this Structure
1LM8 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling., Min JH, Yang H, Ivan M, Gertler F, Kaelin WG Jr, Pavletich NP, Science. 2002 Jun 7;296(5574):1886-9. Epub 2002 May 9. PMID:12004076
Page seeded by OCA on Sun Mar 30 22:04:37 2008
