8W35

Aca2 from Pectobacterium phage ZF40 bound to RNA

8W35 の概要

• エントリーDOI: 10.2210/pdb8w35/pdb
• EMDBエントリー: 43762
• 分子名称: Anti-CRISPR associated (Aca) protein, Aca2, IR2 and IR-RBS RNA (2 entities in total)
• 機能のキーワード: hth protein, crispr, rna-binding protein, rna binding protein
• 由来する生物種: Pectobacterium phage ZF40; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 40883.82

構造登録者

Wilkinson, M.E.,Birkholz, N.,Kimanius, D.,Fineran, P.C. (登録日: 2024-02-21, 公開日: 2024-07-24, 最終更新日: 2024-08-14)

主引用文献

Birkholz, N.,Kamata, K.,Feussner, M.,Wilkinson, M.E.,Cuba Samaniego, C.,Migur, A.,Kimanius, D.,Ceelen, M.,Went, S.C.,Usher, B.,Blower, T.R.,Brown, C.M.,Beisel, C.L.,Weinberg, Z.,Fagerlund, R.D.,Jackson, S.A.,Fineran, P.C.
Phage anti-CRISPR control by an RNA- and DNA-binding helix-turn-helix protein.
Nature, 631:670-677, 2024

PubMed Abstract: In all organisms, regulation of gene expression must be adjusted to meet cellular requirements and frequently involves helix-turn-helix (HTH) domain proteins. For instance, in the arms race between bacteria and bacteriophages, rapid expression of phage anti-CRISPR (acr) genes upon infection enables evasion from CRISPR-Cas defence; transcription is then repressed by an HTH-domain-containing anti-CRISPR-associated (Aca) protein, probably to reduce fitness costs from excessive expression. However, how a single HTH regulator adjusts anti-CRISPR production to cope with increasing phage genome copies and accumulating acr mRNA is unknown. Here we show that the HTH domain of the regulator Aca2, in addition to repressing Acr synthesis transcriptionally through DNA binding, inhibits translation of mRNAs by binding conserved RNA stem-loops and blocking ribosome access. The cryo-electron microscopy structure of the approximately 40 kDa Aca2-RNA complex demonstrates how the versatile HTH domain specifically discriminates RNA from DNA binding sites. These combined regulatory modes are widespread in the Aca2 family and facilitate CRISPR-Cas inhibition in the face of rapid phage DNA replication without toxic acr overexpression. Given the ubiquity of HTH-domain-containing proteins, it is anticipated that many more of them elicit regulatory control by dual DNA and RNA binding.

PubMed: 38987591
DOI: 10.1038/s41586-024-07644-1

実験手法

ELECTRON MICROSCOPY (2.61 Å)