Regulation of the First Committed Step in Lipopolysaccharide Biosynthesis Catalyzed by LpxC Requires the Essential Protein LapC (YejM) and HslVU Protease
| Autor: | Gracjana Klein, Daria Biernacka, Satish Raina, Patrycja Gorzelak |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Threonine Transcription Genetic medicine.medical_treatment Mutant Amino Acid Motifs LapB LapC urologic and male genital diseases Hydroxamic Acids lcsh:Chemistry Suppression Genetic ATP-Dependent Proteases Transcription (biology) Promoter Regions Genetic lcsh:QH301-705.5 Spectroscopy Conserved Sequence Heat-Shock Proteins Phospholipids medicine.diagnostic_test biology YejM Chemistry Escherichia coli Proteins lipopolysaccharide Temperature General Medicine Computer Science Applications Cell biology FabZ Essential gene Periplasm HslV/U protease Proteolysis Protein subunit 030106 microbiology HslVU Catalysis Article LpxC Amidohydrolases Inorganic Chemistry 03 medical and health sciences Protein Domains Operon medicine Escherichia coli Amino Acid Sequence Physical and Theoretical Chemistry Molecular Biology Suppressor mutation Protease RpoE Organic Chemistry 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Mutation biology.protein Biocatalysis |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 21, Iss 9088, p 9088 (2020) Volume 21 Issue 23 |
| ISSN: | 1422-0067 |
| Popis: | We previously showed that lipopolysaccharide (LPS) assembly requires the essential LapB protein to regulate FtsH-mediated proteolysis of LpxC protein that catalyzes the first committed step in the LPS synthesis. To further understand the essential function of LapB and its role in LpxC turnover, multicopy suppressors of &Delta lapB revealed that overproduction of HslV protease subunit prevents its lethality by proteolytic degradation of LpxC, providing the first alternative pathway of LpxC degradation. Isolation and characterization of an extragenic suppressor mutation that prevents lethality of &Delta lapB by restoration of normal LPS synthesis identified a frame-shift mutation after 377 aa in the essential gene designated lapC, suggesting LapB and LapC act antagonistically. The same lapC gene was identified during selection for mutations that induce transcription from LPS defects-responsive rpoEP3 promoter, confer sensitivity to LpxC inhibitor CHIR090 and a temperature-sensitive phenotype. Suppressors of lapC mutants that restored growth at elevated temperatures mapped to lapA/lapB, lpxC and ftsH genes. Such suppressor mutations restored normal levels of LPS and prevented proteolysis of LpxC in lapC mutants. Interestingly, a lapC deletion could be constructed in strains either overproducing LpxC or in the absence of LapB, revealing that FtsH, LapB and LapC together regulate LPS synthesis by controlling LpxC amounts. |
| Databáze: | OpenAIRE |
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