7C0M

Human cGAS-nucleosome complex

7C0M の概要

• エントリーDOI: 10.2210/pdb7c0m/pdb
• EMDBエントリー: 30267
• 分子名称: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (8 entities in total)
• 機能のキーワード: complex, chromatin, ntase, innate immunity, immunity, nucleosome, cgas, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 492271.24

構造登録者

Kujirai, T.,Zierhut, C.,Takizawa, Y.,Kim, R.,Negishi, L.,Uruma, N.,Hirai, S.,Funabiki, H.,Kurumizaka, H. (登録日: 2020-05-01, 公開日: 2020-09-16, 最終更新日: 2024-03-27)

主引用文献

Kujirai, T.,Zierhut, C.,Takizawa, Y.,Kim, R.,Negishi, L.,Uruma, N.,Hirai, S.,Funabiki, H.,Kurumizaka, H.
Structural basis for the inhibition of cGAS by nucleosomes.
Science, 370:455-458, 2020

PubMed Abstract: The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) senses invasion of pathogenic DNA and stimulates inflammatory signaling, autophagy, and apoptosis. Organization of host DNA into nucleosomes was proposed to limit cGAS autoinduction, but the underlying mechanism was unknown. Here, we report the structural basis for this inhibition. In the cryo-electron microscopy structure of the human cGAS-nucleosome core particle (NCP) complex, two cGAS monomers bridge two NCPs by binding the acidic patch of the histone H2A-H2B dimer and nucleosomal DNA. In this configuration, all three known cGAS DNA binding sites, required for cGAS activation, are repurposed or become inaccessible, and cGAS dimerization, another prerequisite for activation, is inhibited. Mutating key residues linking cGAS and the acidic patch alleviates nucleosomal inhibition. This study establishes a structural framework for why cGAS is silenced on chromatinized self-DNA.

PubMed: 32912999
DOI: 10.1126/science.abd0237

実験手法

ELECTRON MICROSCOPY (3.9 Å)