Jaiman Deepika, Persson Karina
Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.
Department of Chemistry, Umeå University, Umeå, Sweden.
Front Microbiol. 2024 Dec 19;15:1512451. doi: 10.3389/fmicb.2024.1512451. eCollection 2024.
Lipoproteins are crucial for maintaining the structural integrity of bacterial membranes. In Gram-negative bacteria, the localization of lipoprotein (Lol) system facilitates the transport of these proteins from the inner membrane to the outer membrane. In , an ε-proteobacterium, lipoprotein transport differs significantly from the canonical and well-studied system in , particularly due to the absence of LolB and the use of a LolF homodimer instead of the LolCE heterodimer. This study presents the crystal structure of the lipoprotein chaperone LolA (LolA-HP) and its interaction with lipopeptide antibiotics such as polymyxin B and colistin. Isothermal titration calorimetry revealed that, unlike LolA from and , LolA-HP does not bind to these antibiotics. Structural comparisons showed that LolA-HP has a deeper hydrophobic cleft but lacks the negative electrostatic potential critical for binding polymyxins. These findings offer insights into the structural diversity of LolA across bacterial species and its potential as a target for antibacterial agents.
脂蛋白对于维持细菌膜的结构完整性至关重要。在革兰氏阴性菌中，脂蛋白定位（Lol）系统有助于这些蛋白质从内膜转运至外膜。在一种ε-变形菌中，脂蛋白转运与经典且研究充分的系统有显著差异，特别是由于缺乏LolB且使用LolF同二聚体而非LolCE异二聚体。本研究展示了ε-变形菌脂蛋白伴侣LolA（LolA-HP）的晶体结构及其与脂肽抗生素如多粘菌素B和黏菌素的相互作用。等温滴定量热法表明，与来自其他菌的LolA不同，LolA-HP不与这些抗生素结合。结构比较显示，LolA-HP有一个更深的疏水裂缝，但缺乏对结合多粘菌素至关重要的负静电势。这些发现为不同细菌物种中LolA的结构多样性及其作为抗菌剂靶点的潜力提供了见解。
