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 (PlzA, B and C) are the only c-di-GMP receptors identified to date and PlzA 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 PlzA in complex with c-di-GMP (1.6 Å resolution). This is the first structure of a xPilz domain in complex with c-di-GMP to be determined. PlzA 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 PlzA 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.

中文翻译：

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与 c-di-GMP 复合的博氏疏螺旋体 PlzA 蛋白的高分辨率晶体结构：对 c-di-GMP 与新型 xPilZ 结构域相互作用的新见解

在蜱传病原体伯氏疏螺旋体和 Hermsii 疏螺旋体中，c-di-GMP 由单一的二鸟苷酸环化酶 (Rrp1) 产生。在这些病原体中，Plz 蛋白（PlzA、B 和 C）是迄今为止鉴定的唯一 c-di-GMP 受体，而 PlzA 是在所有疏螺旋体分离物中发现的唯一 c-di-GMP 受体。生物信息学分析表明，PlzA 具有独特的 PilZN3-PilZ 架构，具有相对不常见的 xPilZ 域。在这里，我们展示了与 c-di-GMP（1.6 Å 分辨率）复合的 PlzA 的晶体结构。这是要确定的与 c-di-GMP 复合的 xPilz 结构域的第一个结构。PlzA 具有双域结构，其中每个域包含拓扑等效的 PilZ 域，具有最小的序列同一性但显着的结构相似性。c-di-GMP 结合位点由连接两个域的链接器形成。虽然无法确定 apo PlzA 的结构，但之前的荧光共振能量转移数据表明，apo 和全息形式的蛋白质在结构上是不同的。从这项研究中获得的信息将有助于正在进行的努力，以确定 PlzA 介导的蜱和哺乳动物调节的分子机制。