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TitleRegulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 4576, Year 2022
Publish dateAug 5, 2022
AuthorsSheng Shu / Wei Mi /
PubMed AbstractLipopolysaccharide (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- ...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.
External linksNat Commun / PubMed:35931690 / PubMed Central
MethodsEM (single particle)
Resolution3.9 - 4.1 Å
Structure data

EMDB-25713, PDB-7t6d:
CryoEM structure of the YejM/LapB complex
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-25731: CryoEM map of the YejM/LapB complex with periplasmic domain
Method: EM (single particle) / Resolution: 4.1 Å

Chemicals

ChemComp-LPP:
2-(HEXADECANOYLOXY)-1-[(PHOSPHONOOXY)METHYL]ETHYL HEXADECANOATE / phospholipid*YM

ChemComp-PGV:
(1R)-2-{[{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL (11E)-OCTADEC-11-ENOATE / phospholipid*YM

Source
  • escherichia coli (E. coli)
KeywordsMEMBRANE PROTEIN / YejM / YciM / regulation / lipopolysaccharide synthesis / LpxC

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