Tools
Tools
Alsaleh, A, Holland, A, Shin, H, Reyes, TP, Baksh, A, Taiwo-Aiyerin, OT, Pigli, Y, Rice, PA and Olorunniji, F (2025) Large serine integrases utilise scavenged phage proteins as directionality cofactors. Nucleic Acids Research (NAR), 53 (3). ISSN 0305-1048
|
Text
gkaf050.pdf - Published Version Available under License Creative Commons Attribution Non-commercial. Download (2MB) | Preview |
Abstract
Recombination directionality factors (RDFs) for large serine integrases (LSIs) are cofactor proteins that control the directionality of recombination to favour excision over insertion. Although RDFs are predicted to bind their cognate LSIs in similar ways, there is no overall common structural theme across LSI RDFs, leading to the suggestion that some of them may be moonlighting proteins with other primary functions. To test this hypothesis, we searched for characterized proteins with structures similar to the predicted structures of known RDFs. Our search shows that the RDFs for two LSIs, TG1 integrase and Bxb1 integrase, show high similarities to a single-stranded DNA binding (SSB) protein and an editing exonuclease, respectively. We present experimental data to show that Bxb1 RDF is probably an exonuclease and TG1 RDF is a functional SSB protein. We used mutational analysis to validate the integrase-RDF interface predicted by AlphaFold2 multimer for TG1 integrase and its RDF, and establish that control of recombination directionality is mediated via protein–protein interaction at the junction of recombinase’s second DNA binding domain and the base of the coiled-coil domain.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 05 Environmental Sciences; 06 Biological Sciences; 08 Information and Computing Sciences; Developmental Biology; 31 Biological sciences; 34 Chemical sciences; 41 Environmental sciences |
| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics |
| Divisions: | Pharmacy and Biomolecular Sciences |
| Publisher: | Oxford University Press |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 05 Feb 2025 12:10 |
| Last Modified: | 05 Feb 2025 12:10 |
| DOI or ID number: | 10.1093/nar/gkaf050 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/25543 |
 |
View Item |