6NT7

Cryo-EM structure of full-length chicken STING in the cGAMP-bound dimeric state

6NT7 の概要

• エントリーDOI: 10.2210/pdb6nt7/pdb
• EMDBエントリー: 0504
• 分子名称: Stimulator of interferon genes protein, cGAMP (2 entities in total)
• 機能のキーワード: er, membrane, adaptor, immune system
• 由来する生物種: Gallus gallus (Chicken)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89088.55

構造登録者

Shang, G.,Zhang, C.,Chen, Z.J.,Bai, X.,Zhang, X. (登録日: 2019-01-28, 公開日: 2019-03-06, 最終更新日: 2024-03-20)

主引用文献

Shang, G.,Zhang, C.,Chen, Z.J.,Bai, X.C.,Zhang, X.
Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP.
Nature, 567:389-393, 2019

PubMed Abstract: Infections by pathogens that contain DNA trigger the production of type-I interferons and inflammatory cytokines through cyclic GMP-AMP synthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds to and activates stimulator of interferon genes (STING; also known as TMEM173, MITA, ERIS and MPYS). STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain. The cytoplasmic domain of STING forms a dimer, which undergoes a conformational change upon binding to cGAMP. However, it remains unclear how this conformational change leads to STING activation. Here we present cryo-electron microscopy structures of full-length STING from human and chicken in the inactive dimeric state (about 80 kDa in size), as well as cGAMP-bound chicken STING in both the dimeric and tetrameric states. The structures show that the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly. Closure of the ligand-binding domain, induced by cGAMP, leads to a 180° rotation of the ligand-binding domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing. This model of STING oligomerization and activation is supported by our structure-based mutational analyses.

PubMed: 30842659
DOI: 10.1038/s41586-019-0998-5

実験手法

ELECTRON MICROSCOPY (4 Å)