Structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein LptM

Summary: Gram-negative bacteria possess an outer membrane (OM) that acts as a barrier against toxic compounds. Lipopolysaccharide (LPS) in the outer leaflet of the OM is crucial for barrier function and is transported to the OM by the LPS transport system. The LPS translocon (the LptDE complex), med...

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Main Authors: Ryoji Miyazaki, Mai Kimoto, Hidetaka Kohga, Tomoya Tsukazaki
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725007843
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author Ryoji Miyazaki
Mai Kimoto
Hidetaka Kohga
Tomoya Tsukazaki
author_facet Ryoji Miyazaki
Mai Kimoto
Hidetaka Kohga
Tomoya Tsukazaki
author_sort Ryoji Miyazaki
collection DOAJ
description Summary: Gram-negative bacteria possess an outer membrane (OM) that acts as a barrier against toxic compounds. Lipopolysaccharide (LPS) in the outer leaflet of the OM is crucial for barrier function and is transported to the OM by the LPS transport system. The LPS translocon (the LptDE complex), mediates LPS assembly into the OM. Recently, the small lipoprotein LptM was identified as an LptDE interactor that facilitates LptD maturation. However, its mechanism remains unclear. Here, we investigate the detailed interaction between LptM and LptD. We find that LptM interacts with the folded LptD intermediate at the late stage of its maturation. Mutational analyses demonstrate that the N-terminal conserved region of LptM is essential for its function. Cryoelectron microscopy structural analysis of the Escherichia coli LptDEM complex, combined with biochemical analyses, reveals the molecular basis of the LptM-LptD interaction and its functional importance. Thus, we propose that LptM stabilizes LptD for proper assembly.
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spelling doaj-art-94e3b5a02470461ab923306fdbc5562c2025-07-17T04:44:17ZengElsevierCell Reports2211-12472025-08-01448116013Structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein LptMRyoji Miyazaki0Mai Kimoto1Hidetaka Kohga2Tomoya Tsukazaki3Nara Institute of Science and Technology, Nara, Japan; Corresponding authorNara Institute of Science and Technology, Nara, JapanNara Institute of Science and Technology, Nara, JapanNara Institute of Science and Technology, Nara, Japan; Corresponding authorSummary: Gram-negative bacteria possess an outer membrane (OM) that acts as a barrier against toxic compounds. Lipopolysaccharide (LPS) in the outer leaflet of the OM is crucial for barrier function and is transported to the OM by the LPS transport system. The LPS translocon (the LptDE complex), mediates LPS assembly into the OM. Recently, the small lipoprotein LptM was identified as an LptDE interactor that facilitates LptD maturation. However, its mechanism remains unclear. Here, we investigate the detailed interaction between LptM and LptD. We find that LptM interacts with the folded LptD intermediate at the late stage of its maturation. Mutational analyses demonstrate that the N-terminal conserved region of LptM is essential for its function. Cryoelectron microscopy structural analysis of the Escherichia coli LptDEM complex, combined with biochemical analyses, reveals the molecular basis of the LptM-LptD interaction and its functional importance. Thus, we propose that LptM stabilizes LptD for proper assembly.http://www.sciencedirect.com/science/article/pii/S2211124725007843CP: Molecular biologyCP: Microbiology
spellingShingle Ryoji Miyazaki
Mai Kimoto
Hidetaka Kohga
Tomoya Tsukazaki
Structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein LptM
Cell Reports
CP: Molecular biology
CP: Microbiology
title Structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein LptM
title_full Structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein LptM
title_fullStr Structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein LptM
title_full_unstemmed Structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein LptM
title_short Structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein LptM
title_sort structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein lptm
topic CP: Molecular biology
CP: Microbiology
url http://www.sciencedirect.com/science/article/pii/S2211124725007843
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