Borrelia burgdorferi PlzA is a cyclic-di-GMP dependent DNA and RNA binding protein

Nerina Jusufovic, Andrew C. Krusenstjerna, Christina R. Savage, Timothy C. Saylor, Catherine A. Brissette, Wolfram R. Zückert, Paula J. Schlax, Md A. Motaleb, Brian Stevenson

Research output: Contribution to journalArticlepeer-review


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 binding 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.

Original languageEnglish
Pages (from-to)1039-1062
Number of pages24
JournalMolecular Microbiology
Issue number5
StatePublished - May 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.


  • Borrelia
  • DNA-binding protein
  • Lyme disease
  • cyclic-di-GMP

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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