Deciphering the molecular basis of lipoprotein recognition and transport by LolCDE  

作　　者：Wen Qiao Chongrong Shen Yujiao Chen Shenghai Chang Xin Wang Lili Yang Jie Pang Qinghua Luo Zhibo Zhang Yingxin Xiang Chao Zhao Guangwen Lu Bi-Sen Ding Binwu Ying Xiaodi Tang Haohao Dong 

机构地区：[1]Department of Laboratory Medicine,State Key Laboratory of Biotherapy,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University and Collaborative Innovation Center of Biotherapy,Chengdu,China [2]Frontiers Medical Center,Tianfu Jincheng Laboratory,West China Hospital,Sichuan University,Chengdu,China [3]Center of Cryo Electron Microscopy,Zhejiang University,Hangzhou,China

出　　处：《Signal Transduction and Targeted Therapy》2025年第1期434-445,共12页信号转导与靶向治疗(英文)

基　　金：supported by the National Key Research and Development Program of China(2021YFA1301900 to H.D.);the National Natural Science Foundation of China(31900039 and 32170029 to X.T.,32000844 to S.C.,81971974 and 82372297 to H.D.);the 1.3.5 Project for Disciplines Excellence of West China Hospital,Sichuan University(ZYYC23014 to H.D.);the Sichuan Provincial Natural Science Foundation Outstanding Young Scientist Fund Project(2024NSFJQ0002 to H.D.).

摘　　要：Outer membrane(OM)lipoproteins serve vital roles in Gram-negative bacteria,contributing to their pathogenicity and drug resistance.For these lipoproteins to function,they must be transported from the inner membrane(IM),where they are assembled,to the OM by the ABC transporter LolCDE.We have previously captured structural snapshots of LolCDE in multiple states,revealing its dynamic conformational changes.However,the exact mechanism by which LolCDE recognizes and transfers lipoprotein between domains remains unclear.Here,we characterized the E.coli LolCDE complex bound with endogenous lipoprotein or ATP to explore the molecular features governing its substrate binding and transport functions.We found that the N-terminal unstructured linker of lipoprotein is critical for efficient binding by LolCDE;it must be sufficiently long to keep the lipoprotein’s main body outside the complex while allowing the triacyl chains to bind within the central cavity.Mutagenic assays identified key residues that mediate allosteric communication between the cytoplasmic and transmembrane domains and in the periplasmic domain to form a lipoprotein transport pathway at the LolC-LolE interface.This study provides insights into the OM lipoprotein relocation process mediated by LolCDE,with significant implications for antimicrobial drug development.

关 键 词：functions. OUTSIDE CHAINS 

分 类 号：O62[理学—有机化学]