8PE3

Structure of Csm6' from Streptococcus thermophilus in complex with cyclic hexa-adenylate (cA6)

8PE3 の概要

• エントリーDOI: 10.2210/pdb8pe3/pdb
• 関連するPDBエントリー: 8PCW
• 分子名称: CRISPR system endoribonuclease Csm6', Cyclic hexaadenosine monophosphate (cA6), RNA, ... (4 entities in total)
• 機能のキーワード: carf, hepn, ca6, rnase, rna binding protein
• 由来する生物種: Streptococcus thermophilus; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 93988.14

構造登録者

McQuarrie, S.J.,Athukoralage, J.S.,McMahon, S.A.,Graham, S.,Ackerman, K.,Bode, B.E.,White, M.F.,Gloster, T.M. (登録日: 2023-06-13, 公開日: 2023-10-04, 最終更新日: 2023-11-08)

主引用文献

McQuarrie, S.,Athukoralage, J.S.,McMahon, S.A.,Graham, S.,Ackermann, K.,Bode, B.E.,White, M.F.,Gloster, T.M.
Activation of Csm6 ribonuclease by cyclic nucleotide binding: in an emergency, twist to open.
Nucleic Acids Res., 51:10590-10605, 2023

PubMed Abstract: Type III CRISPR systems synthesize cyclic oligoadenylate (cOA) second messengers as part of a multi-faceted immune response against invading mobile genetic elements (MGEs). cOA activates non-specific CRISPR ancillary defence nucleases to create a hostile environment for MGE replication. Csm6 ribonucleases bind cOA using a CARF (CRISPR-associated Rossmann Fold) domain, resulting in activation of a fused HEPN (Higher Eukaryotes and Prokaryotes Nucleotide binding) ribonuclease domain. Csm6 enzymes are widely used in a new generation of diagnostic assays for the detection of specific nucleic acid species. However, the activation mechanism is not fully understood. Here we characterised the cyclic hexa-adenylate (cA6) activated Csm6' ribonuclease from the industrially important bacterium Streptococcus thermophilus. Crystal structures of Csm6' in the inactive and cA6 bound active states illuminate the conformational changes which trigger mRNA destruction. Upon binding of cA6, there is a close to 60° rotation between the CARF and HEPN domains, which causes the 'jaws' of the HEPN domain to open and reposition active site residues. Key to this transition is the 6H domain, a right-handed solenoid domain connecting the CARF and HEPN domains, which transmits the conformational changes for activation.

PubMed: 37747760
DOI: 10.1093/nar/gkad739

実験手法

X-RAY DIFFRACTION (1.96 Å)