控制铜绿假单胞菌生物膜扩散调节因子 RbdA 的磷酸二酯酶活性。

IF 4.2 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Charlotte Cordery, Jack Craddock, Martin Malý, Kieran Basavaraja, Jeremy S. Webb, Martin A. Walsh and Ivo Tews
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引用次数: 0

摘要

浮游生物和生物膜生活方式之间的转换与细胞内第二信使双(3'-5')环二聚体单磷酸鸟苷(c-di-GMP)的浓度有关。虽然细菌拥有环化酶和磷酸二酯酶来催化 c-di-GMP 的形成或水解,但这两种酶域往往出现在同一种蛋白质中。人们默认两种酶活性中的一种占主导地位,其他结构域和蛋白质相互作用可对环境条件做出反应并控制活性。在这里,我们报告了膜蛋白 RbdA(生物膜扩散调节因子)的磷酸二酯酶结构域在二聚活化状态下的结构,并表明磷酸二酯酶的活性是由连接的环化酶控制的。螺旋 α5/α6 周围的磷酸二酯酶区域形成了二聚体界面,为活化提供了理论依据,因为在之前描述的自动抑制结构中,该区域与环化酶结构域接触。动力学分析支持这一模型,因为当磷酸二酯酶与环化酶连接时,单独磷酸二酯酶的活性较低。对 RbdA 外膜结构域计算模型的分析表明,该结构域为全螺旋结构,有一个大的结合口袋,可以容纳假定的配体。揭示 RbdA 等多结构域磷酸二酯酶的调控回路对于开发操纵或驱散细菌生物膜的策略非常重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Control of phosphodiesterase activity in the regulator of biofilm dispersal RbdA from Pseudomonas aeruginosa†

Control of phosphodiesterase activity in the regulator of biofilm dispersal RbdA from Pseudomonas aeruginosa†

Control of phosphodiesterase activity in the regulator of biofilm dispersal RbdA from Pseudomonas aeruginosa†

The switch between planktonic and biofilm lifestyle correlates with intracellular concentration of the second messenger bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP). While bacteria possess cyclase and phosphodiesterase enzymes to catalyse formation or hydrolysis of c-di-GMP, both enzymatic domains often occur in a single protein. It is tacitly assumed that one of the two enzymatic activities is dominant, and that additional domains and protein interactions enable responses to environmental conditions and control activity. Here we report the structure of the phosphodiesterase domain of the membrane protein RbdA (regulator of biofilm dispersal) in a dimeric, activated state and show that phosphodiesterase activity is controlled by the linked cyclase. The phosphodiesterase region around helices α5/α6 forms the dimer interface, providing a rationale for activation, as this region was seen in contact with the cyclase domain in an auto-inhibited structure previously described. Kinetic analysis supports this model, as the activity of the phosphodiesterase alone is lower when linked to the cyclase. Analysis of a computed model of the RbdA periplasmatic domain reveals an all-helical architecture with a large binding pocket that could accommodate putative ligands. Unravelling the regulatory circuits in multi-domain phosphodiesterases like RbdA is important to develop strategies to manipulate or disperse bacterial biofilms.

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来源期刊
CiteScore
6.10
自引率
0.00%
发文量
128
审稿时长
10 weeks
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