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

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.

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 Mon Nov 12 18:41:11 2007