6SCF

A viral anti-CRISPR subverts type III CRISPR immunity by rapid degradation of cyclic oligoadenylate

6SCF の概要

• エントリーDOI: 10.2210/pdb6scf/pdb
• 関連するPDBエントリー: 2x4i
• 分子名称: Uncharacterized protein, cyclic oligoadenylate (3 entities in total)
• 機能のキーワード: crispr cyclic oligoadenylate dna anti-crispr viral, dna
• 由来する生物種: Sulfolobus islandicus rod-shaped virus 1; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 134747.09

構造登録者

McMahon, S.A.,Athukoralage, J.S.,Graham, S.,White, M.F.,Gloster, T.M. (登録日: 2019-07-24, 公開日: 2019-10-30, 最終更新日: 2024-10-16)

主引用文献

Athukoralage, J.S.,McMahon, S.A.,Zhang, C.,Gruschow, S.,Graham, S.,Krupovic, M.,Whitaker, R.J.,Gloster, T.M.,White, M.F.
An anti-CRISPR viral ring nuclease subverts type III CRISPR immunity.
Nature, 577:572-575, 2020

PubMed Abstract: The CRISPR system in bacteria and archaea provides adaptive immunity against mobile genetic elements. Type III CRISPR systems detect viral RNA, resulting in the activation of two regions of the Cas10 protein: an HD nuclease domain (which degrades viral DNA) and a cyclase domain (which synthesizes cyclic oligoadenylates from ATP). Cyclic oligoadenylates in turn activate defence enzymes with a CRISPR-associated Rossmann fold domain, sculpting a powerful antiviral response that can drive viruses to extinction. Cyclic nucleotides are increasingly implicated in host-pathogen interactions. Here we identify a new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA). The viral ring nuclease AcrIII-1 is widely distributed in archaeal and bacterial viruses and in proviruses. The enzyme uses a previously unknown fold to bind cA specifically, and a conserved active site to rapidly cleave this signalling molecule, allowing viruses to neutralize the type III CRISPR defence system. The AcrIII-1 family has a broad host range, as it targets cA signalling molecules rather than specific CRISPR effector proteins. Our findings highlight the crucial role of cyclic nucleotide signalling in the conflict between viruses and their hosts.

PubMed: 31942067
DOI: 10.1038/s41586-019-1909-5

実験手法

X-RAY DIFFRACTION (1.55 Å)