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

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 LptB<sub>2</sub>FGCADE complex. These observations provide initial evidence of functional overlap between the Lpt and Lol pathways, potentially broadening current perspectives on lipoprotein sorting.

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Publication Details

Journal
Nature Communications
Published
2025-05-10
DOI
https://doi.org/10.1038/s41467-025-59660-y
Citations
9
Primary Topic
Genomics and Phylogenetic Studies
Type
article
Field-Weighted Citation Impact
7.25

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article

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

Cheng-ai Wang, Xiaoguang Lei, Shuai Qiao, Michael Hennig et al.
9 citations
Nature Communications
Genomics and Phylogenetic Studies
7.25
article

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

Cheng-ai Wang, Xiaoguang Lei, Shuai Qiao, Michael Hennig, Wonpil Im, Lianwan Chen, Qingshan Luo, Yihua Huang, Jizhong Lou, Seonghoon Kim, Min Zhou, Weiwei Bei, Long Miao, Shan Yu, Fan Wu, Kun Wang, Yong Zhang, Jiangge Zheng
article en
9 citations

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 LptB<sub>2</sub>FGCADE complex. These observations provide initial evidence of functional overlap between the Lpt and Lol pathways, potentially broadening current perspectives on lipoprotein sorting.

Nature CommunicationsVol. 16(1)
Zhejiang International Studies University (CN), Fuyang Normal University (CN), Lehigh University (US), Chinese Academy of Sciences (CN), Beijing Normal University (CN), Wenzhou Medical University (CN), Nanjing University of Science and Technology (CN), Institute of Biophysics (CN), Beijing National Laboratory for Molecular Sciences (CN), University of Chinese Academy of Sciences (CN)
National Science Foundation, Emory University, Salt Science Research Foundation, University of Oxford, Chinese Academy of Sciences, Ministry of Science and Technology of the People's Republic of China, School of Medicine, Emory University, Institute of Biophysics, Chinese Academy of Sciences
Zero hunger
Openalex Percentile: Top 3%
Genomics and Phylogenetic Studies
7.25
DOIOpen Access PDFOpenAlex
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