6WT6

Structure of a metazoan TIR-STING receptor from C. gigas

6WT6 の概要

• エントリーDOI: 10.2210/pdb6wt6/pdb
• 分子名称: Metazoan TIR-STING fusion (2 entities in total)
• 機能のキーワード: tir domain, cyclic dinucleotide receptor, immune effector, immune system
• 由来する生物種: Crassostrea gigas
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47063.29

構造登録者

Morehouse, B.R.,Govande, A.A.,Millman, A.,Keszei, A.F.A.,Lowey, B.,Ofir, G.,Shao, S.,Sorek, R.,Kranzusch, P.J. (登録日: 2020-05-01, 公開日: 2020-09-09, 最終更新日: 2024-03-06)

主引用文献

Morehouse, B.R.,Govande, A.A.,Millman, A.,Keszei, A.F.A.,Lowey, B.,Ofir, G.,Shao, S.,Sorek, R.,Kranzusch, P.J.
STING cyclic dinucleotide sensing originated in bacteria.
Nature, 586:429-433, 2020

PubMed Abstract: Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides that are released during bacterial infection and in endogenous cyclic GMP-AMP signalling during viral infection and anti-tumour immunity. STING shares no structural homology with other known signalling proteins, which has limited attempts at functional analysis and prevented explanation of the origin of cyclic dinucleotide signalling in mammalian innate immunity. Here we reveal functional STING homologues encoded within prokaryotic defence islands, as well as a conserved mechanism of signal activation. Crystal structures of bacterial STING define a minimal homodimeric scaffold that selectively responds to cyclic di-GMP synthesized by a neighbouring cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme. Bacterial STING domains couple the recognition of cyclic dinucleotides with the formation of protein filaments to drive oligomerization of TIR effector domains and rapid NAD cleavage. We reconstruct the evolutionary events that followed the acquisition of STING into metazoan innate immunity, and determine the structure of a full-length TIR-STING fusion from the Pacific oyster Crassostrea gigas. Comparative structural analysis demonstrates how metazoan-specific additions to the core STING scaffold enabled a switch from direct effector function to regulation of antiviral transcription. Together, our results explain the mechanism of STING-dependent signalling and reveal the conservation of a functional cGAS-STING pathway in prokaryotic defence against bacteriophages.

PubMed: 32877915
DOI: 10.1038/s41586-020-2719-5

実験手法

X-RAY DIFFRACTION (2.41 Å)