生物发生
易位
肽
化学
分子动力学
生物物理学
抗菌肽
细菌外膜
细胞生物学
生物化学
生物
膜
膜蛋白
大肠杆菌
基因
计算化学
作者
Francesco Fiorentino,Joshua B. Sauer,Xingyu Qiu,Robin A. Corey,C. Keith Cassidy,Benjamin Mynors-Wallis,Shahid Mehmood,Jani Reddy Bolla,Phillip J. Stansfeld,Carol V. Robinson
标识
DOI:10.1038/s41589-020-00694-2
摘要
Lipopolysaccharide (LPS) transport to the outer membrane (OM) is a crucial step in the biogenesis of microbial surface defenses. Although many features of the translocation mechanism have been elucidated, molecular details of LPS insertion via the LPS transport (Lpt) OM protein LptDE remain elusive. Here, we integrate native MS with hydrogen-deuterium exchange MS and molecular dynamics simulations to investigate the influence of substrate and peptide binding on the conformational dynamics of LptDE. Our data reveal that LPS induces opening of the LptD β-taco domain, coupled with conformational changes on β-strands adjacent to the putative lateral exit gate. Conversely, an antimicrobial peptide, thanatin, stabilizes the β-taco, thereby preventing LPS transport. Our results illustrate that LPS insertion into the OM relies on concerted opening movements of both the β-barrel and β-taco domains of LptD, and suggest a means for developing antimicrobial therapeutics targeting this essential process in Gram-negative ESKAPE pathogens.
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