Balanced biosynthesis of major membrane components through regulated degradation of the committed enzyme of lipid A biosynthesis by the AAA protease FtsH (HflB) in Escherichia coli.
The suppressor mutation, named sfhC21, that allows Escherichia coli ftsH null mutant cells to survive was found to be an allele of fabZ encoding R-3-hydroxyacyl-ACP dehydrase, involved in a key step of fatty acid biosynthesis, and appears to upregulate the dehydrase. The ftsH1(Ts) mutation increased the amount of lipopolysaccharide at 42 degrees C. This was accompanied by a dramatic increase in the amount of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase [the IpxC (envA) gene product] involved in the committed step of lipid A biosynthesis. Pulse-chase experiments and in vitro assays with purified components showed that FtsH, the AAA-type membrane-bound metalloprotease, degrades the deacetylase. Genetic evidence also indicated that the FtsH protease activity for the deacetylase might be affected when acyl-ACP pools were altered. The biosynthesis of phospholipids and the lipid A moiety of lipopolysaccharide, both of which derive their fatty acyl chains from the same R-3-hydroxyacyl-ACP pool, is regulated by FtsH.
Department of Molecular Cell Biology, Kumamoto University School of Medicine, Japan. ogura@gpo.kumamoto-u.ac.jp
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Inoue
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Tatsuta
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Suzaki
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Karata
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Fierke
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Jackman
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Raetz
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Coleman
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Tomoyasu
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Matsuzawa
D049069:ATP-Dependent Proteases; D000581:Amidohydrolases / Q000032:analysis / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D002462:Cell Membrane / Q000648:ultrastructure; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D005838:Genotype; D008050:Lipid A / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000032:analysis; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D008854:Microscopy, Electron; D008954:Models, Biological; D016296:Mutagenesis; D010641:Phenotype; D011233:Precipitin Tests; D013696:Temperature; D013997:Time Factors
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008050:Lipid A; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D049069:ATP-Dependent Proteases; C513383:FtsH protein, E coli; D000581:Amidohydrolases; C097307:UDP-3-O-acyl-N-acetylglucosamine deacetylase