4ZP4

Crystal Structure of the Heterodimeric HIF-2a:ARNT Complex

4ZP4 の概要

• エントリーDOI: 10.2210/pdb4zp4/pdb
• 関連するPDBエントリー: 4ZPH 4ZPK 4ZPR
• 分子名称: Aryl hydrocarbon receptor nuclear translocator, Endothelial PAS domain-containing protein 1 (3 entities in total)
• 機能のキーワード: arnt, hif-2a complex, bhlh-pas, protein transport-transcription complex, protein transport/transcription
• 由来する生物種: Mus musculus (Mouse); 詳細
• 細胞内の位置: Nucleus: P53762 P97481
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 169276.69

構造登録者

Wu, D.,Potluri, N.,Lu, J.,Kim, Y.,Rastinejad, F. (登録日: 2015-05-07, 公開日: 2015-08-12, 最終更新日: 2023-09-27)

主引用文献

Wu, D.,Potluri, N.,Lu, J.,Kim, Y.,Rastinejad, F.
Structural integration in hypoxia-inducible factors.
Nature, 524:303-308, 2015

PubMed Abstract: The hypoxia-inducible factors (HIFs) coordinate cellular adaptations to low oxygen stress by regulating transcriptional programs in erythropoiesis, angiogenesis and metabolism. These programs promote the growth and progression of many tumours, making HIFs attractive anticancer targets. Transcriptionally active HIFs consist of HIF-α and ARNT (also called HIF-1β) subunits. Here we describe crystal structures for each of mouse HIF-2α-ARNT and HIF-1α-ARNT heterodimers in states that include bound small molecules and their hypoxia response element. A highly integrated quaternary architecture is shared by HIF-2α-ARNT and HIF-1α-ARNT, wherein ARNT spirals around the outside of each HIF-α subunit. Five distinct pockets are observed that permit small-molecule binding, including PAS domain encapsulated sites and an interfacial cavity formed through subunit heterodimerization. The DNA-reading head rotates, extends and cooperates with a distal PAS domain to bind hypoxia response elements. HIF-α mutations linked to human cancers map to sensitive sites that establish DNA binding and the stability of PAS domains and pockets.

PubMed: 26245371
DOI: 10.1038/nature14883

実験手法

X-RAY DIFFRACTION (2.355 Å)