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1p97

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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'''
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===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.
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(as it appears on PubMed at http://www.pubmed.gov), where 14668441 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14668441}}
==Disease==
==Disease==
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==About this Structure==
==About this Structure==
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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].
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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].
==Reference==
==Reference==
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[[Category: Karakuzu, O.]]
[[Category: Karakuzu, O.]]
[[Category: Mixed alpha-beta fold]]
[[Category: Mixed alpha-beta fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:50:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:02:06 2008''

Revision as of 16:02, 27 July 2008

Image:1p97.png

Template:STRUCTURE 1p97

Contents

NMR structure of the C-terminal PAS domain of HIF2a

Template:ABSTRACT PUBMED 14668441

Disease

Known disease associated with this structure: Erythrocytosis, familial, 4 OMIM:[603349]

About this Structure

1P97 is a Single protein structure of sequence from Homo sapiens. Full experimental 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

Page seeded by OCA on Sun Jul 27 19:02:06 2008

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