Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector
Abstract Bacterial CBASS immune defense systems commonly kill virally infected cells by degrading genomic DNA in a form of cell suicide or abortive infection. We present a high-resolution structure of the CBASS effector Cap5, activated by a cyclic nucleotide, in the act of digesting DNA via tetramer...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-06-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60484-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849469860238589952 |
|---|---|
| author | Olga Rechkoblit Daniela Sciaky Mi Ni Yangmei Li Jithesh Kottur Gang Fang Aneel K. Aggarwal |
| author_facet | Olga Rechkoblit Daniela Sciaky Mi Ni Yangmei Li Jithesh Kottur Gang Fang Aneel K. Aggarwal |
| author_sort | Olga Rechkoblit |
| collection | DOAJ |
| description | Abstract Bacterial CBASS immune defense systems commonly kill virally infected cells by degrading genomic DNA in a form of cell suicide or abortive infection. We present a high-resolution structure of the CBASS effector Cap5, activated by a cyclic nucleotide, in the act of digesting DNA via tetrameric HNH endonuclease domains. Two HNH domains are in a catalytically active state for cleavage of the DNA strands, whereas the other two HNH domains are in a topologically distinct catalytically inactive state for simply DNA binding. The four HNH domains track one face of the DNA and mark an enzyme that acts as a stand-alone non-specific nuclease. We also show that chromosomally encoded CBASS Cap5 can be extrinsically activated by a cyclic nucleotide, as a step towards potential antibiotics. |
| format | Article |
| id | doaj-art-7e6fba9d79244ca79fb3e00e60f48168 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7e6fba9d79244ca79fb3e00e60f481682025-08-20T03:25:19ZengNature PortfolioNature Communications2041-17232025-06-011611910.1038/s41467-025-60484-zMechanism of DNA degradation by CBASS Cap5 endonuclease immune effectorOlga Rechkoblit0Daniela Sciaky1Mi Ni2Yangmei Li3Jithesh Kottur4Gang Fang5Aneel K. Aggarwal6Department of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount SinaiAbstract Bacterial CBASS immune defense systems commonly kill virally infected cells by degrading genomic DNA in a form of cell suicide or abortive infection. We present a high-resolution structure of the CBASS effector Cap5, activated by a cyclic nucleotide, in the act of digesting DNA via tetrameric HNH endonuclease domains. Two HNH domains are in a catalytically active state for cleavage of the DNA strands, whereas the other two HNH domains are in a topologically distinct catalytically inactive state for simply DNA binding. The four HNH domains track one face of the DNA and mark an enzyme that acts as a stand-alone non-specific nuclease. We also show that chromosomally encoded CBASS Cap5 can be extrinsically activated by a cyclic nucleotide, as a step towards potential antibiotics.https://doi.org/10.1038/s41467-025-60484-z |
| spellingShingle | Olga Rechkoblit Daniela Sciaky Mi Ni Yangmei Li Jithesh Kottur Gang Fang Aneel K. Aggarwal Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector Nature Communications |
| title | Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector |
| title_full | Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector |
| title_fullStr | Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector |
| title_full_unstemmed | Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector |
| title_short | Mechanism of DNA degradation by CBASS Cap5 endonuclease immune effector |
| title_sort | mechanism of dna degradation by cbass cap5 endonuclease immune effector |
| url | https://doi.org/10.1038/s41467-025-60484-z |
| work_keys_str_mv | AT olgarechkoblit mechanismofdnadegradationbycbasscap5endonucleaseimmuneeffector AT danielasciaky mechanismofdnadegradationbycbasscap5endonucleaseimmuneeffector AT mini mechanismofdnadegradationbycbasscap5endonucleaseimmuneeffector AT yangmeili mechanismofdnadegradationbycbasscap5endonucleaseimmuneeffector AT jitheshkottur mechanismofdnadegradationbycbasscap5endonucleaseimmuneeffector AT gangfang mechanismofdnadegradationbycbasscap5endonucleaseimmuneeffector AT aneelkaggarwal mechanismofdnadegradationbycbasscap5endonucleaseimmuneeffector |