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标题：Structural basis of lipoprotein recognition by the bacterial Lol trafficking chaperone LolA
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作者：Elise Kaplan ; Nicholas P. Greene ; Abigail E. Jepson 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：36
DOI：10.1073/pnas.2208662119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance Lipoproteins in gram-negative bacteria underpin the formation and maintenance of the outer membrane that constitutes a vital protective barrier against antibiotics and other noxious molecules. An essential transport system comprising the LolABCDE proteins is required to traffic lipoproteins to the outer membrane. Following maturation on the inner membrane and extraction by the LolCDE transporter, lipoproteins are passed to the chaperone LolA that carries them across the periplasm prior to insertion into the outer membrane by the LolB receptor. Here, we report the molecular details of lipoprotein interaction with the chaperone LolA, a key intermediate located at the heart of the Lol pathway. The structure provides valuable insights into this important system and could be exploited to develop new antimicrobials. In gram-negative bacteria, lipoproteins are vital structural components of the outer membrane (OM) and crucial elements of machineries central to the physiology of the cell envelope. A dedicated apparatus, the Lol system, is required for the correct localization of OM lipoproteins and is essential for viability. The periplasmic chaperone LolA is central to this trafficking pathway, accepting triacylated lipoproteins from the inner membrane transporter LolCDE, before carrying them across the periplasm to the OM receptor LolB. Here, we report a crystal structure of liganded LolA, generated in vivo, revealing the molecular details of lipoprotein association. The structure highlights how LolA, initially primed to receive lipoprotein by interaction with LolC, further opens to accommodate the three ligand acyl chains in a precise conformation within its cavity. LolA forms extensive interactions with the acyl chains but not with any residue of the cargo, explaining the chaperone’s ability to transport structurally diverse lipoproteins. Structural characterization of a ligandedLolA variant incapable of lipoprotein release reveals aberrant association, demonstrating the importance of the LolCDE-coordinated, sequential opening of LolA for inserting lipoprotein in a manner productive for subsequent trafficking. Comparison with existing structures of LolA in complex with LolC or LolCDE reveals substantial overlap of the lipoprotein and LolC binding sites within the LolA cavity, demonstrating that insertion of lipoprotein acyl chains physically disengages the chaperone protein from the transporter by perturbing interaction with LolC. Taken together, our data provide a key step toward a complete understanding of a fundamentally important trafficking pathway.
关键词：enLol lipoprotein traffickingprotein–lipid interactionX-ray crystallographyABC transporterantibacterial target