GGDEF-EAL 结构域包含 c-di-GMP 受体 FimX 的结构分析。

Structural analysis of the GGDEF-EAL domain-containing c-di-GMP receptor FimX.

机构信息

Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

出版信息

Structure. 2009 Aug 12;17(8):1104-16. doi: 10.1016/j.str.2009.06.010.

Bacterial pathogenesis involves social behavior including biofilm formation and swarming, processes that are regulated by the bacterially unique second messenger cyclic di-GMP (c-di-GMP). Diguanylate cyclases containing GGDEF and phosphodiesterases containing EAL domains have been identified as the enzymes controlling cellular c-di-GMP levels, yet less is known regarding signal transmission and the targets of c-di-GMP. FimX, a protein from Pseudomonas aeruginosa that governs twitching motility, belongs to a large subfamily containing both GGDEF and EAL domains. Biochemical and structural analyses reveals its function as a high-affinity receptor for c-di-GMP. A model for full-length FimX was generated combining solution scattering data and crystal structures of the degenerate GGDEF and EAL domains. Although FimX forms a dimer in solution via the N-terminal domains, a crystallographic EAL domain dimer suggests modes for the regulation of FimX by c-di-GMP binding. The results provide the structural basis for c-di-GMP sensing via degenerate phosphodiesterases.

细菌发病机制涉及包括生物膜形成和群集运动在内的社会行为，这些过程受细菌特有的第二信使环二鸟苷酸（c-di-GMP）调控。已经鉴定出含有 GGDEF 结构域的环二鸟苷酸环化酶和含有 EAL 结构域的磷酸二酯酶作为控制细胞内 c-di-GMP 水平的酶，然而对于信号转导和 c-di-GMP 的靶标知之甚少。铜绿假单胞菌中控制菌毛运动的蛋白 FimX 属于含有 GGDEF 和 EAL 结构域的大亚家族。生化和结构分析揭示了其作为 c-di-GMP 高亲和力受体的功能。通过结合溶液散射数据和退化 GGDEF 和 EAL 结构域的晶体结构，生成了全长 FimX 的模型。尽管 FimX 在溶液中通过 N 端结构域形成二聚体，但晶体学 EAL 结构域二聚体表明 c-di-GMP 结合对 FimX 调节的模式。该结果为通过退化磷酸二酯酶进行 c-di-GMP 感应提供了结构基础。