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Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli
Lipopolysaccharide (LPS) is an essential glycolipid and forms a protective permeability barrier for most Gram-negative bacteria. In E. coli, LPS levels are under feedback control, achieved by FtsH-mediated degradation of LpxC, which catalyzes the first committed step in LPS synthesis. FtsH is a memb...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356133/ https://www.ncbi.nlm.nih.gov/pubmed/35931690 http://dx.doi.org/10.1038/s41467-022-32277-1 |
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author | Shu, Sheng Mi, Wei |
author_facet | Shu, Sheng Mi, Wei |
author_sort | Shu, Sheng |
collection | PubMed |
description | Lipopolysaccharide (LPS) is an essential glycolipid and forms a protective permeability barrier for most Gram-negative bacteria. In E. coli, LPS levels are under feedback control, achieved by FtsH-mediated degradation of LpxC, which catalyzes the first committed step in LPS synthesis. FtsH is a membrane-bound AAA+ protease, and its protease activity toward LpxC is regulated by essential membrane proteins LapB and YejM. However, the regulatory mechanisms are elusive. We establish an in vitro assay to analyze the kinetics of LpxC degradation and demonstrate that LapB is an adaptor protein that utilizes its transmembrane helix to interact with FtsH and its cytoplasmic domains to recruit LpxC. Our YejM/LapB complex structure reveals that YejM is an anti-adaptor protein, competing with FtsH for LapB to inhibit LpxC degradation. Structural analysis unravels that LapB and LPS have overlapping binding sites in YejM. Thus, LPS levels control formation of the YejM/LapB complex to determine LpxC protein levels. |
format | Online Article Text |
id | pubmed-9356133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93561332022-08-07 Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli Shu, Sheng Mi, Wei Nat Commun Article Lipopolysaccharide (LPS) is an essential glycolipid and forms a protective permeability barrier for most Gram-negative bacteria. In E. coli, LPS levels are under feedback control, achieved by FtsH-mediated degradation of LpxC, which catalyzes the first committed step in LPS synthesis. FtsH is a membrane-bound AAA+ protease, and its protease activity toward LpxC is regulated by essential membrane proteins LapB and YejM. However, the regulatory mechanisms are elusive. We establish an in vitro assay to analyze the kinetics of LpxC degradation and demonstrate that LapB is an adaptor protein that utilizes its transmembrane helix to interact with FtsH and its cytoplasmic domains to recruit LpxC. Our YejM/LapB complex structure reveals that YejM is an anti-adaptor protein, competing with FtsH for LapB to inhibit LpxC degradation. Structural analysis unravels that LapB and LPS have overlapping binding sites in YejM. Thus, LPS levels control formation of the YejM/LapB complex to determine LpxC protein levels. Nature Publishing Group UK 2022-08-05 /pmc/articles/PMC9356133/ /pubmed/35931690 http://dx.doi.org/10.1038/s41467-022-32277-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Shu, Sheng Mi, Wei Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli |
title | Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli |
title_full | Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli |
title_fullStr | Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli |
title_full_unstemmed | Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli |
title_short | Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli |
title_sort | regulatory mechanisms of lipopolysaccharide synthesis in escherichia coli |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356133/ https://www.ncbi.nlm.nih.gov/pubmed/35931690 http://dx.doi.org/10.1038/s41467-022-32277-1 |
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