High-resolution crystal structure of the Borreliella burgdorferi PlzA protein in complex with c-di-GMP: new insights into the interaction of c-d GMP with the novel xPilZ domain

In the tick-borne pathogens, Borreliella burgdorferi and Borrelia hermsii, c-di-GMP is produced by a single diguanylate cyclase (Rrp1). In these pathogens, the Plz proteins (PIzA, B and C) are the only c-di-GMP receptors identified to date and PIzA is the sole c-di-GMP receptor found in all Borreliella isolates. Bioinformatic analyses suggest that PlzA has a unique PilZN3-PilZ architecture with the relatively uncommon xPilZ domain. Here, we present the crystal structure of PIzA in complex with c-di-GMP (1.6 A resolution). This is the first structure of a xPilz domain in complex with c-di-GMP to be determined. PIzA has a two-domain structure, where each domain comprises topologically equivalent PilZ domains with minimal sequence identity but remarkable structural similarity. The c-di-GMP binding site is formed by the linker connecting the two domains. While the structure of apo PIzA could not be determined, previous fluorescence resonance energy transfer data suggest that apo and holo forms of the protein are structurally distinct. The information obtained from this study will facilitate ongoing efforts to identify the molecular mechanisms of PlzA-mediated regulation in ticks and mammals.

Automated summary

This study presents the crystal structure of PIzA in complex with c-di-GMP, revealing its unique two-domain structure and the mechanism of c-di-GMP binding site formation. The information obtained will facilitate further research on the regulatory mechanisms of PlzA in ticks and mammals.