1p97

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 1p97 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 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

Page seeded by OCA on Fri Feb 15 16:39:19 2008