Architecture et Fonction des Macromolécules Biologiques, UMR6098, CNRS et Universités Aix-Marseille I et II, 163 avenue de Luminy, 13288 Marseille, France.
Environ Microbiol. 2010 Jun;12(6):1775-86. doi: 10.1111/j.1462-2920.2010.02264.x.
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.
细菌双组分调控系统（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 来说，刺激是一种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央 TCS GacA/GacS 进行通信，拮抗地介导生物膜形成。最近，研究表明 RetS 通过形成 RetS/GacS 异源二聚体来调节 GacS 传感器的活性。LadS 和 RetS 是混合传感器，其信号域由 7 个跨膜（7TMR）区域和一个周质传感器域（不同的细胞内信号模块细胞外 2，DISMED2）组成。RetS DISMED2 的 2.65Å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 结构还显示了两个假定的配体结合位点。一个与结构相关的碳水化合物结合模块（CBM）中的类似位点相当，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，并提供了有关配体结合如何调节 RetS 同源二聚化以控制 RetS/GacS 异源二聚体形成的线索。对 LadS 的 DISMED2 进行建模揭示了仅保守一个配体结合位点，这表明该传感器激酶的活性具有独特的机制。
