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

The PilZ domain-containing protein, PlzA, is the only cyclic di-GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in the regulation of many borrelial processes, but the functional mechanism of PlzA was not previously known. We report that PlzA can bind DNA and RNA within the promoter and 5' UTR of the glycerol metabolism operon, glpFKD , and that nucleic acid binding requires c-di-GMP. In the presence of c-di-GMP, PlzA formed multimeric complexes with nucleic acids. PlzA contains two PilZ domains. Dissection of the domains demonstrated that the separated N-terminal domain bound nucleic acids in a c-di-GMP-independent manner. The C-terminal domain, which includes the c-di-GMP binding motif, did not bind nucleic acids under any tested conditions. Structural modeling suggests that c-di-GMP binding to the C-terminal domain stabilizes interactions between the two domains, facilitating nucleic acid binding through residues in the N-terminal domain.