Abstract
MucA and MucB are critical negative modulators of sigma factor AlgU and regulate the mucoid conversion of Pseudomonas aeruginosa. Previous studies have revealed that lipid signals antagonize MucA-MucB binding. Here we report the crystal structure of MucB in complex with the periplasmic domain of MucA and polyethylene glycol (PEG), which unveiled an intermediate state preceding the MucA-MucB dissociation. Based on the biochemical experiments, the aliphatic side chain with a polar group was found to be of primary importance for inducing MucA cleavage. These results provide evidence that the hydrophobic cavity of MucB is a primary site for sensing lipid molecules and illustrates the detailed control of conformational switching within MucA-MucB in response to lipophilic effectors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence / genetics
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Bacterial Proteins / chemistry
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Bacterial Proteins / genetics*
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Bacterial Proteins / ultrastructure*
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Crystallography, X-Ray
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Gene Expression Regulation, Bacterial / genetics
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Hydrophobic and Hydrophilic Interactions
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Lipids / chemistry
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Lipids / genetics
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Mutation / genetics
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Polyethylene Glycols / chemistry
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Protein Binding / genetics
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Protein Conformation
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Pseudomonas aeruginosa / chemistry
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Pseudomonas aeruginosa / pathogenicity
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Pseudomonas aeruginosa / ultrastructure*
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Sigma Factor / chemistry
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Sigma Factor / genetics*
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Sigma Factor / ultrastructure*
Substances
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AlgU protein, Pseudomonas aeruginosa
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Bacterial Proteins
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Lipids
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MucA protein, Pseudomonas
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Sigma Factor
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algN protein, Pseudomonas aeruginosa
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Polyethylene Glycols