Molecular basis of the lipid-induced MucA-MucB dissociation in Pseudomonas aeruginosa
Molecular basis of the lipid-induced MucA-MucB dissociation in Pseudomonas aeruginosa
复制标题
铜绿假单胞菌中脂质诱导的 MucA-MucB 解离的分子基础。
DOI：
10.1038/s42003-020-01147-1
复制
发表时间：
2020-08-03
影响因子：
5.9
通讯作者：
Bao，Rui
中科院分区：
文献类型：
--
作者：
Li，Tao;He，Lihui;Bao，Rui
粘蛋白A和粘蛋白B是Sigma因子alu的关键负调制子，调节铜绿假单胞菌的粘液转化。先前的研究表明，脂质信号拮抗粘蛋白A和粘蛋白B的结合。本文报道了粘蛋白A与聚乙二醇(PEG)形成的复合体中粘蛋白B的晶体结构，揭示了粘蛋白A与粘蛋白B解离前的中间态。生化实验表明，含极性基团的脂肪族侧链对诱导粘蛋白A的裂解起主要作用。这些结果提供了证据，证明MucB的疏水空腔是感测脂分子的主要部位，并说明了亲脂效应物对MucA-MucB内构象转换的详细控制。
MucA and MucB are critical negative modulators of sigma factor AlgU and regulate the mucoid conversion ofPseudomonas aeruginosa. Previous studies have revealed that lipid signals antagonize MucA-MucB binding. Here we report the crystal structure of MucB in complex with the periplasmic domain of MucA and polyethylene glycol (PEG), which unveiled an intermediate state preceding the MucA-MucB dissociation. Based on the biochemical experiments, the aliphatic side chain with a polar group was found to be of primary importance for inducing MucA cleavage. These results provide evidence that the hydrophobic cavity of MucB is a primary site for sensing lipid molecules and illustrates the detailed control of conformational switching within MucA-MucB in response to lipophilic effectors.