8B0U

Structure of the CalpL/T10 complex

8B0U の概要

• エントリーDOI: 10.2210/pdb8b0u/pdb
• 分子名称: SAVED domain-containing protein, CalpT10, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: protease, crispr type iii, coa, ca4, peptide binding protein, hydrolase
• 由来する生物種: Sulfurihydrogenibium; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 133995.92

構造登録者

Schneberger, N.,Hagelueken, G. (登録日: 2022-09-08, 公開日: 2022-11-16, 最終更新日: 2024-02-07)

主引用文献

Rouillon, C.,Schneberger, N.,Chi, H.,Blumenstock, K.,Da Vela, S.,Ackermann, K.,Moecking, J.,Peter, M.F.,Boenigk, W.,Seifert, R.,Bode, B.E.,Schmid-Burgk, J.L.,Svergun, D.,Geyer, M.,White, M.F.,Hagelueken, G.
Antiviral signalling by a cyclic nucleotide activated CRISPR protease.
Nature, 614:168-174, 2023

PubMed Abstract: CRISPR defence systems such as the well-known DNA-targeting Cas9 and the RNA-targeting type III systems are widespread in prokaryotes. The latter orchestrates a complex antiviral response that is initiated through the synthesis of cyclic oligoadenylates after recognition of foreign RNA. Among the large set of proteins that are linked to type III systems and predicted to bind cyclic oligoadenylates, a CRISPR-associated Lon protease (CalpL) stood out to us. CalpL contains a sensor domain of the SAVED family fused to a Lon protease effector domain. However, the mode of action of this effector is unknown. Here we report the structure and function of CalpL and show that this soluble protein forms a stable tripartite complex with two other proteins, CalpT and CalpS, that are encoded on the same operon. After activation by cyclic tetra-adenylate (cA), CalpL oligomerizes and specifically cleaves the MazF homologue CalpT, which releases the extracytoplasmic function σ factor CalpS from the complex. Our data provide a direct connection between CRISPR-based detection of foreign nucleic acids and transcriptional regulation. Furthermore, the presence of a SAVED domain that binds cyclic tetra-adenylate in a CRISPR effector reveals a link to the cyclic-oligonucleotide-based antiphage signalling system.

PubMed: 36423657
DOI: 10.1038/s41586-022-05571-7

実験手法

X-RAY DIFFRACTION (3.29 Å)