8PKI

Cryo-EM structure of NR5A2-nucleosome complex SHL+5.5

8PKI の概要

• エントリーDOI: 10.2210/pdb8pki/pdb
• EMDBエントリー: 17740
• 分子名称: Histone H3.3, Histone H4, Histone H2A, ... (8 entities in total)
• 機能のキーワード: nucleosome, nuclear receptor, nr5a2, dna binding protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 215229.85

構造登録者

Kobayashi, W.,Sappler, A.,Bollschweiler, D.,Kummecke, M.,Basquin, J.,Arslantas, E.,Ruangroengkulrith, S.,Hornberger, R.,Duderstadt, K.,Tachibana, K. (登録日: 2023-06-26, 公開日: 2024-02-28, 最終更新日: 2024-05-29)

主引用文献

Kobayashi, W.,Sappler, A.H.,Bollschweiler, D.,Kummecke, M.,Basquin, J.,Arslantas, E.N.,Ruangroengkulrith, S.,Hornberger, R.,Duderstadt, K.,Tachibana, K.
Nucleosome-bound NR5A2 structure reveals pioneer factor mechanism by DNA minor groove anchor competition.
Nat.Struct.Mol.Biol., 31:757-766, 2024

PubMed Abstract: Gene expression during natural and induced reprogramming is controlled by pioneer transcription factors that initiate transcription from closed chromatin. Nr5a2 is a key pioneer factor that regulates zygotic genome activation in totipotent embryos, pluripotency in embryonic stem cells and metabolism in adult tissues, but the mechanism of its pioneer activity remains poorly understood. Here, we present a cryo-electron microscopy structure of human NR5A2 bound to a nucleosome. The structure shows that the conserved carboxy-terminal extension (CTE) loop of the NR5A2 DNA-binding domain competes with a DNA minor groove anchor of the nucleosome and releases entry-exit site DNA. Mutational analysis showed that NR5A2 D159 of the CTE is dispensable for DNA binding but required for stable nucleosome association and persistent DNA 'unwrapping'. These findings suggest that NR5A2 belongs to an emerging class of pioneer factors that can use DNA minor groove anchor competition to destabilize nucleosomes and facilitate gene expression during reprogramming.

PubMed: 38409506
DOI: 10.1038/s41594-024-01239-0

実験手法

ELECTRON MICROSCOPY (2.58 Å)