Nature Communications, 10 May, 2025, DOI：https://doi.org/10.1038/s41467-025-59660-y

Surface lipoprotein sorting by crosstalk between Lpt and Lol pathways in gram-negative bacteria

Qingshan Luo, Chengai Wang, Shuai Qiao, Shan Yu, Lianwan Chen, Seonghoon Kim, Kun Wang, Jiangge Zheng, Yong Zhang, Fan Wu, Xiaoguang Lei, Jizhong Lou, Michael Hennig, Wonpil Im, Long Miao, Min Zhou, Weiwei Bei & Yihua Huang

Abstract

Lipopolysaccharide (LPS) and lipoprotein, two essential components of the outer membrane (OM) in Gram-negative bacteria, play critical roles in bacterial physiology and pathogenicity. LPS translocation to the OM is mediated by LptDE, yet how lipoproteins sort to the cell surface remains elusive. Here, we identify candidate lipoproteins that may be transported to the cell surface via LptDE. Notably, we determine the crystal structures of LptDE from Pseudomonas aeruginosa and its complex with an endogenous Escherichia coli lipoprotein LptM. The paLptDE-LptM structure demonstrates that LptM may translocate to the OM via LptDE, in a manner similar to LPS transport. The β-barrel domain serves as a passage for the proteinaceous moiety while its acyl chains are transported outside. Our finding has been corroborated by results from native mass spectrometry, immunofluorescence, and photocrosslinking assays, revealing a potential surface exposed lipoproteins (SLPs) transport mechanism through which lipoproteins are loaded into LptA by LolCDE prior to assembly of the LptB₂FGCADE complex. These observations provide initial evidence of functional overlap between the Lpt and Lol pathways, potentially broadening current perspectives on lipoprotein sorting.

Artcicle link：https://www.nature.com/articles/s41467-025-59660-y