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| Title | Dual function of LapB (YciM) in regulating lipopolysaccharide synthesis. |
|---|---|
| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 121, Issue 17, Page e2321510121, Year 2024 |
| Publish date | Apr 23, 2024 |
 Authors | Sheng Shu / Yuko Tsutsui / Rajkanwar Nathawat / Wei Mi /  |
| PubMed Abstract | Levels of lipopolysaccharide (LPS), an essential glycolipid on the surface of most gram-negative bacteria, are tightly controlled-making LPS synthesis a promising target for developing new ...Levels of lipopolysaccharide (LPS), an essential glycolipid on the surface of most gram-negative bacteria, are tightly controlled-making LPS synthesis a promising target for developing new antibiotics. adaptor protein LapB (YciM) plays an important role in regulating LPS synthesis by promoting degradation of LpxC, a deacetylase that catalyzes the first committed step in LPS synthesis. Under conditions where LPS is abundant, LapB recruits LpxC to the AAA+ protease FtsH for degradation. LapB achieves this by simultaneously interacting with FtsH through its transmembrane helix and LpxC through its cytoplasmic domain. Here, we describe a cryo-EM structure of the complex formed between LpxC and the cytoplasmic domain of LapB (LapB). The structure reveals how LapB exploits both its tetratricopeptide repeat (TPR) motifs and rubredoxin domain to interact with LpxC. Through both in vitro and in vivo analysis, we show that mutations at the LapB/LpxC interface prevent LpxC degradation. Unexpectedly, binding to LapB also inhibits the enzymatic activity of LpxC through allosteric effects reminiscent of LpxC activation by MurA in Our findings argue that LapB regulates LPS synthesis in two steps: In the first step, LapB inhibits the activity of LpxC, and in the second step, it commits LpxC to degradation by FtsH. |
 External links | Proc Natl Acad Sci U S A / PubMed:38635633 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.6 Å |
| Structure data | EMDB-42897, PDB-8v24: |
| Chemicals |  ChemComp-ZN:  ChemComp-24G:  ChemComp-ACT: |
| Source |
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 Keywords |  PROTEIN BINDING / adaptor / complex / deacetylase / LPS / LpxC / LapB(YciM) |
