Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli
Abstract 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...
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Nature Portfolio
2022-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-32277-1 |
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| author | Sheng Shu Wei Mi |
| author_facet | Sheng Shu Wei Mi |
| author_sort | Sheng Shu |
| collection | DOAJ |
| description | Abstract 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 | Article |
| id | doaj-art-d283d1891ba64155b2b2bf9e4df23f94 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d283d1891ba64155b2b2bf9e4df23f942025-08-20T03:53:22ZengNature PortfolioNature Communications2041-17232022-08-0113111110.1038/s41467-022-32277-1Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coliSheng Shu0Wei Mi1Department of Pharmacology, Yale University School of MedicineDepartment of Pharmacology, Yale University School of MedicineAbstract 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.https://doi.org/10.1038/s41467-022-32277-1 |
| spellingShingle | Sheng Shu Wei Mi Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli Nature Communications |
| 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 |
| url | https://doi.org/10.1038/s41467-022-32277-1 |
| work_keys_str_mv | AT shengshu regulatorymechanismsoflipopolysaccharidesynthesisinescherichiacoli AT weimi regulatorymechanismsoflipopolysaccharidesynthesisinescherichiacoli |