1P97

NMR structure of the C-terminal PAS domain of HIF2a

1P97 の概要

• エントリーDOI: 10.2210/pdb1p97/pdb
• 分子名称: Endothelial PAS domain protein 1 (1 entity in total)
• 機能のキーワード: mixed alpha-beta fold, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (Potential): Q99814
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13192.98

構造登録者

Erbel, P.J.,Card, P.B.,Karakuzu, O.,Bruick, R.K.,Gardner, K.H. (登録日: 2003-05-09, 公開日: 2004-01-13, 最終更新日: 2024-05-22)

主引用文献

Erbel, P.J.,Card, P.B.,Karakuzu, O.,Bruick, R.K.,Gardner, K.H.
Structural basis for PAS domain heterodimerization in the basic helix-loop-helix-PAS transcription factor hypoxia-inducible factor.
Proc.Natl.Acad.Sci.USA, 100:15504-15509, 2003

PubMed Abstract: 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.

PubMed: 14668441
DOI: 10.1073/pnas.2533374100

実験手法

SOLUTION NMR