1p97

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spinqualitylabelsall models PDB ID 1p97 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
Gene:	EPAS1 (Homo sapiens)
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

NMR structure of the C-terminal PAS domain of HIF2a

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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 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 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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