1p97
From Proteopedia
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- | [[Image:1p97.jpg|left|200px]] | + | [[Image:1p97.jpg|left|200px]] |
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- | '''NMR structure of the C-terminal PAS domain of HIF2a''' | + | {{Structure |
+ | |PDB= 1p97 |SIZE=350|CAPTION= <scene name='initialview01'>1p97</scene> | ||
+ | |SITE= | ||
+ | |LIGAND= | ||
+ | |ACTIVITY= | ||
+ | |GENE= EPAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
+ | }} | ||
+ | |||
+ | '''NMR structure of the C-terminal PAS domain of HIF2a''' | ||
+ | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
- | 1P97 is a [ | + | 1P97 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P97 OCA]. |
==Reference== | ==Reference== | ||
- | Structural basis for PAS domain heterodimerization in the basic helix--loop--helix-PAS transcription factor hypoxia-inducible factor., Erbel PJ, Card PB, Karakuzu O, Bruick RK, Gardner KH, Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15504-9. Epub 2003 Dec 10. PMID:[http:// | + | Structural basis for PAS domain heterodimerization in the basic helix--loop--helix-PAS transcription factor hypoxia-inducible factor., Erbel PJ, Card PB, Karakuzu O, Bruick RK, Gardner KH, Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15504-9. Epub 2003 Dec 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14668441 14668441] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: mixed alpha-beta fold]] | [[Category: mixed alpha-beta fold]] | ||
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:21:31 2008'' |
Revision as of 11:21, 20 March 2008
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Gene: | EPAS1 (Homo sapiens) | ||||||
Coordinates: | save as pdb, mmCIF, xml |
NMR structure of the C-terminal PAS domain of HIF2a
Contents |
Overview
Biological responses to oxygen availability play important roles in development, physiological homeostasis, and many disease processes. In mammalian cells, this adaptation is mediated in part by a conserved pathway centered on the hypoxia-inducible factor (HIF). HIF is a heterodimeric protein complex composed of two members of the basic helix-loop-helix Per-ARNT-Sim (PAS) (ARNT, aryl hydrocarbon receptor nuclear translocator) domain family of transcriptional activators, HIFalpha and ARNT. Although this complex involves protein-protein interactions mediated by basic helix-loop-helix and PAS domains in both proteins, the role played by the PAS domains is poorly understood. To address this issue, we have studied the structure and interactions of the C-terminal PAS domain of human HIF-2alpha by NMR spectroscopy. We demonstrate that HIF-2alpha PAS-B binds the analogous ARNT domain in vitro, showing that residues involved in this interaction are located on the solvent-exposed side of the HIF-2alpha central beta-sheet. Mutating residues at this surface not only disrupts the interaction between isolated PAS domains in vitro but also interferes with the ability of full-length HIF to respond to hypoxia in living cells. Extending our findings to other PAS domains, we find that this beta-sheet interface is widely used for both intra- and intermolecular interactions, suggesting a basis of specificity and regulation of many types of PAS-containing signaling proteins.
Disease
Known diseases associated with this structure: Erythrocytosis, familial, 4 OMIM:[603349]
About this Structure
1P97 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for PAS domain heterodimerization in the basic helix--loop--helix-PAS transcription factor hypoxia-inducible factor., Erbel PJ, Card PB, Karakuzu O, Bruick RK, Gardner KH, Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15504-9. Epub 2003 Dec 10. PMID:14668441
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