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| [[Image:1p97.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1p97| PDB=1p97 | SCENE= }} | | {{STRUCTURE_1p97| PDB=1p97 | SCENE= }} |
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| '''NMR structure of the C-terminal PAS domain of HIF2a'''
| | ===NMR structure of the C-terminal PAS domain of HIF2a=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_14668441}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 14668441 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_14668441}} |
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| ==Disease== | | ==Disease== |
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| ==About this Structure== | | ==About this Structure== |
| 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]. | | 1P97 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P97 OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Karakuzu, O.]] | | [[Category: Karakuzu, O.]] |
| [[Category: Mixed alpha-beta fold]] | | [[Category: Mixed alpha-beta fold]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:50:29 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:02:06 2008'' |
