Molecular basis of the lipid-induced MucA-MucB dissociation in Pseudomonas aeruginosa.

Li, Tao; He, Lihui; Li, Changcheng; Kang, Mei; Song, Yingjie; Zhu, Yibo; Shen, Yalin; Zhao, Ninglin; Zhao, Chang; Yang, Jing; Huang, Qin; Mou, Xingyu; Tong, Aiping; Yang, Jinliang; Wang, Zhenling; Ji, Chengjie; Li, Hong; Tang, Hong; Bao, Rui

MucA and MucB are critical negative modulators of sigma factor AlgU and regulate the mucoid conversion of Pseudomonas 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.