8W35
Aca2 from Pectobacterium phage ZF40 bound to RNA
Summary for 8W35
| Entry DOI | 10.2210/pdb8w35/pdb |
| EMDB information | 43762 |
| Descriptor | Anti-CRISPR associated (Aca) protein, Aca2, IR2 and IR-RBS RNA (2 entities in total) |
| Functional Keywords | hth protein, crispr, rna-binding protein, rna binding protein |
| Biological source | Pectobacterium phage ZF40 More |
| Total number of polymer chains | 3 |
| Total formula weight | 40883.82 |
| Authors | Wilkinson, M.E.,Birkholz, N.,Kimanius, D.,Fineran, P.C. (deposition date: 2024-02-21, release date: 2024-07-24, Last modification date: 2024-08-14) |
| Primary citation | 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 Cited by 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: 38987591DOI: 10.1038/s41586-024-07644-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.61 Å) |
Structure validation
Download full validation report
