Distinct oligomeric forms of the Pseudomonas aeruginosa RetS sensor domain modulate accessibility to the ligand binding site.
Distinct oligomeric forms of the Pseudomonas aeruginosa RetS sensor domain modulate accessibility to the ligand binding site.
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DOI：
10.1111/j.1462-2920.2010.02264.x
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发表时间：
2009-08
影响因子：
5.1
通讯作者：
F. Vincent;A. Round;A. Reynaud;Christophe Bordi;A. Filloux;Y. Bourne
中科院分区：
文献类型：
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作者：
F. Vincent;A. Round;A. Reynaud;Christophe Bordi;A. Filloux;Y. Bourne
细菌双组分调节系统（TCS）感知环境刺激以适应微生物种群的生活方式。对于许多TCS，刺激物是未知化学性质的配体。铜绿假单胞菌利用密切相关的RetS和LadS传感器激酶在急性和慢性感染之间切换。这些传感器蛋白通过与中心TCS GacA/GacS通信拮抗性地介导生物膜形成。最近，研究表明RetS通过形成RetS/GacS异二聚体来调节GacS传感器活性。LadS和RetS是具有由7-跨膜（7 TMR）区域和周质传感器结构域（多样的细胞内信号传导模块胞外2，DISMED 2）组成的信号传导结构域的混合传感器。RetS DISMED 2的2.65 A分辨率晶体结构，称为RetSp，揭示了三种不同的寡聚状态，能够进行结构域交换。RetSp结构还显示两个推定的配体结合位点。一个相当于结构相关的碳水化合物结合模块（CBM）中的类似位点，但第二个位点位于二聚体界面。这些观察结果突出了RetSp折叠的模块化结构和组装，并提供了如何在配体结合后调节RetS的同源二聚化以控制RetS/GacS异源二聚体的形成的线索。对LadS的DISMED 2进行建模揭示了仅一个配体结合位点的保守性，这表明该传感器激酶的活性具有独特的机制。
Bacterial two-component regulatory systems (TCSs) sense environmental stimuli to adapt the lifestyle of microbial populations. For many TCSs the stimulus is a ligand of unknown chemical nature. Pseudomonas aeruginosa utilizes the closely related RetS and LadS sensor kinases to switch between acute and chronic infections. These sensor proteins antagonistically mediate biofilm formation through communication with a central TCS, GacA/GacS. Recently, it was shown that RetS modulates the GacS sensor activity by forming RetS/GacS heterodimers. LadS and RetS are hybrid sensors with a signalling domain consisting of a 7-transmembrane (7TMR) region and a periplasmic sensor domain (diverse intracellular signalling module extracellular 2, DISMED2). The 2.65 A resolution crystal structure of RetS DISMED2, called RetSp, reveals three distinct oligomeric states capable of domain swapping. The RetSp structure also displays two putative ligand binding sites. One is equivalent to the analogous site in the structurally-related carbohydrate binding module (CBM) but the second site is located at a dimer interface. These observations highlight the modular architecture and assembly of the RetSp fold and give clues on how homodimerization of RetS could be modulated upon ligand binding to control formation of a RetS/GacS heterodimer. Modelling the DISMED2 of LadS reveals conservation of only one ligand binding site, suggesting a distinct mechanism underlying the activity of this sensor kinase.