Abstract
The PilZ domain-containing protein, PlzA, is the only known cyclic di- GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in the regulation of many borrelial processes, but the effector mechanism of PlzA was not previously known. Here, we report that PlzA can bind DNA and RNA and that nucleic acid binding requires c-di-GMP, with the affinity of PlzA for nucleic acids increasing as concentrations of c-di-GMP were increased. A mutant PlzA that is incapable of bind- ing c-di-GMP did not bind to any tested nucleic acids. We also determined that PlzA interacts predominantly with the major groove of DNA and that sequence length and G–C content play a role in DNA binding affinity. PlzA is a dual-domain protein with a PilZ-like N-terminal domain linked to a canonical C-terminal PilZ domain. Dissection of the domains demonstrated that the separated N-terminal domain bound nucleic acids independently of c-di-GMP. The C-terminal domain, which includes the c-di- GMP binding motifs, did not bind nucleic acids under any tested conditions. Our data are supported by computational docking, which predicts that c-di-GMP binding at the C-terminal domain stabilizes the overall protein structure and facilitates PlzA-DNA interactions via residues in the N-terminal domain. Based on our data, we propose that levels of c-di-GMP during the various stages of the enzootic life cycle direct PlzA binding to regulatory targets.
Document Type
Article
Publication Date
3-2024
Digital Object Identifier (DOI)
https://doi.org/10.1111/mmi.15254
Funding Information
National Institutes of Health, Grant/ Award Number: R01 AI144126-3
Repository Citation
Jusufovic, Nerina; Krusenstjerna, Andrew; Savage, Christina R.; Saylor, Timothy C.; Brissette, Catherine A.; Zückert, Wolfram; Schlax, Paula J.; Motaleb, Md A.; and Stevenson, Brian, "Borrelia burgdorferi PlzA is a cyclic-di-GMP dependent DNA and RNA binding protein" (2024). Entomology Faculty Publications. 239.
https://uknowledge.uky.edu/entomology_facpub/239
Notes/Citation Information
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2024 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.