3F1P

Crystal structure of a high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains

3F1P の概要

• エントリーDOI: 10.2210/pdb3f1p/pdb
• 関連するPDBエントリー: 1P97 1X0O 2A24 2B02 3F1N 3F1O
• 分子名称: Endothelial PAS domain-containing protein 1, Aryl hydrocarbon receptor nuclear translocator (3 entities in total)
• 機能のキーワード: pas domain, heterodimer, internal cavity, activator, angiogenesis, congenital erythrocytosis, developmental protein, differentiation, disease mutation, dna-binding, hydroxylation, nucleus, phosphoprotein, transcription, transcription regulation, ubl conjugation, alternative splicing, polymorphism
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus : Q99814 P27540
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27781.40

構造登録者

Scheuermann, T.H.,Tomchick, D.R.,Machius, M.,Guo, Y.,Bruick, R.K.,Gardner, K.H. (登録日: 2008-10-28, 公開日: 2009-01-20, 最終更新日: 2023-09-06)

主引用文献

Scheuermann, T.H.,Tomchick, D.R.,Machius, M.,Guo, Y.,Bruick, R.K.,Gardner, K.H.
Artificial ligand binding within the HIF2alpha PAS-B domain of the HIF2 transcription factor.
Proc.Natl.Acad.Sci.USA, 106:450-455, 2009

PubMed Abstract: The hypoxia-inducible factor (HIF) basic helix-loop-helix Per-aryl hydrocarbon receptor nuclear translocator (ARNT)-Sim (bHLH-PAS) transcription factors are master regulators of the conserved molecular mechanism by which metazoans sense and respond to reductions in local oxygen concentrations. In humans, HIF is critically important for the sustained growth and metastasis of solid tumors. Here, we describe crystal structures of the heterodimer formed by the C-terminal PAS domains from the HIF2alpha and ARNT subunits of the HIF2 transcription factor, both in the absence and presence of an artificial ligand. Unexpectedly, the HIF2alpha PAS-B domain contains a large internal cavity that accommodates ligands identified from a small-molecule screen. Binding one of these ligands to HIF2alpha PAS-B modulates the affinity of the HIF2alpha:ARNT PAS-B heterodimer in vitro. Given the essential role of PAS domains in forming active HIF heterodimers, these results suggest a presently uncharacterized ligand-mediated mechanism for regulating HIF2 activity in endogenous and clinical settings.

PubMed: 19129502
DOI: 10.1073/pnas.0808092106

実験手法

X-RAY DIFFRACTION (1.17 Å)