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

Structural analysis of the GGDEF-EAL domain-containing c-di-GMP receptor FimX.
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DOI:
10.1016/j.str.2009.06.010
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发表时间:
2009-08-12
期刊:
Structure (London, England : 1993)
影响因子:
--
通讯作者:
Sondermann H
Sondermann H
中科院分区:
其他
文献类型:
--
作者:
Navarro MV;De N;Bae N;Wang Q;Sondermann H

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细菌发病机制涉及社会行为,包括生物膜形成和群集,这些过程由细菌独特的第二信使环二-GMP(c-di-GMP)调节。含有GGDEF的二鸟苷酸环化酶和含有EAL结构域的磷酸二酯酶已被鉴定为控制细胞c-di-GMP水平的酶,但关于信号传递和c-di-GMP的靶点知之甚少。FimX是一种来自绿脓杆菌的蛋白质,其控制抽搐运动,属于包含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的高亲和力受体的功能。结合溶液散射数据和退化GGDEF和EAL域的晶体结构,生成全长FimX的模型。虽然FimX通过N-末端结构域在溶液中形成二聚体,但晶体学EAL结构域二聚体表明通过c-di-GMP结合调节FimX的模式。这些结果为通过简并磷酸二酯酶进行c-di-GMP传感提供了结构基础。
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. While 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.
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