The adaptability of the ion binding site by the Ag(I)/Cu(I) periplasmic chaperone SilF

Lithgo, Ryan M.; Hanževački, Marko; Harris, Gemma; Kamps, Jos J .A. G.; Holden, Ellie; Gianga, Tiberiu-Marius; Benesch, Justin L.P.; Jäger, Christof M.; Croft, Anna K.; Hussain, Rohannah; Hobman, Jon L.; Orville, Allen M.; Quigley, Andrew; Carr, Stephen B.; Scott, David J.

Abstract

The periplasmic chaperone SilF has been identified as part of an Ag(I) detoxification system in Gram negative bacteria. Sil proteins also bind Cu(I), but with reported weaker affinity, therefore leading to the designation of a specific detoxification system for Ag(I). Using isothermal titration calorimetry we show that binding of both ions is not only tighter than previously thought, but of very similar affinities. We investigated the structural origins of ion binding using molecular dynamics and QM/MM simulations underpinned by structural and biophysical experiments. The results of this analysis showed that the binding site adapts to accommodate either ion, with key interactions with the solvent in the case of Cu(I). The implications of this are that Gram negative bacteria do not appear to have evolved a specific Ag(I) efflux system but take advantage of the existing Cu(I) detoxification system. Therefore, there are consequences for how we define a particular metal resistance mechanism and understand its evolution in the environment.

Citation

Lithgo, R. M., Hanževački, M., Harris, G., Kamps, J. J. .. G., Holden, E., Gianga, T.-M., Benesch, J. L., Jäger, C. M., Croft, A. K., Hussain, R., Hobman, J. L., Orville, A. M., Quigley, A., Carr, S. B., & Scott, D. J. (2023). The adaptability of the ion binding site by the Ag(I)/Cu(I) periplasmic chaperone SilF. Journal of Biological Chemistry, 299(11), Article 105331. https://doi.org/10.1016/j.jbc.2023.105331

• Journal Article Type: Article
• Acceptance Date: Oct 4, 2023
• Online Publication Date: Nov 1, 2023
• Publication Date: Nov 1, 2023
• Deposit Date: Oct 27, 2023
• Publicly Available Date: Nov 7, 2023
• Journal: Journal of Biological Chemistry
• Print ISSN: 0021-9258
• Electronic ISSN: 1083-351X
• Publisher: American Society for Biochemistry and Molecular Biology
• Peer Reviewed: Peer Reviewed
• Volume: 299
• Issue: 11
• Article Number: 105331
• DOI: https://doi.org/10.1016/j.jbc.2023.105331
• Keywords: Silver ion binding, QM-MM, metal ion chaperone, structural biology, thermodynamic
• Public URL: https://nottingham-repository.worktribe.com/output/26262283
• Publisher URL: https://www.jbc.org/article/S0021-9258(23)02359-1/fulltext
• Additional Information: This article is maintained by: Elsevier; Article Title: The adaptability of the ion binding site by the Ag(I)/Cu(I) periplasmic chaperone SilF.; Journal Title: Journal of Biological Chemistry; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jbc.2023.105331; Content Type: article; Copyright: © 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.