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• W2079146663 startingPage "385" @default.
• W2079146663 abstract "The resistance-nodulation-cell division family multidrug transporter Acriflavine resistance protein B (AcrB) from Eschericha coli is an obligate homotrimer. Approximately, 45% of the inter-subunit interface is contributed by a protruding loop (also referred to as the thumb) and its corresponding binding tunnel in the neighboring subunit. In an earlier study, we have demonstrated that a single Pro to Gly mutation in the loop drastically destabilized AcrB trimer and reduced its substrate efflux activity. To further dissect the role of the loop during AcrB trimerization, we performed Ala scanning of the loop and examined the effect of each mutation on protein activity. We found that not all conserved residues are important for AcrB function and likewise not all critical residues are conserved. In addition, we replaced the loop of AcrB with the loop of MexB, which is a highly conserved homolog of AcrB. The resultant chimeric protein remained partly active. Structural characterization of the chimeric protein indicated that it was well folded and existed as a mixture of monomer and trimer. Our results indicate that the loop to tunnel interaction, while critical to trimerization and efflux function, is in general rather flexible and tolerant to mutations. In addition, all mutations in the loop that resulted in reduced function clustered closely, suggesting that this may be the site of inter-subunit recognition during trimerization and/or a locking zone to stabilize the inter-subunit interaction during trimerization." @default.
• W2079146663 created "2016-06-24" @default.
• W2079146663 creator A5008077107 @default.
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• W2079146663 creator A5042971747 @default.
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• W2079146663 date "2013-04-01" @default.
• W2079146663 modified "2023-09-26" @default.
• W2079146663 title "Dissecting the function of a protruding loop in AcrB trimerization" @default.
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• W2079146663 doi "https://doi.org/10.1080/07391102.2012.703065" @default.
• W2079146663 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22877148" @default.
• W2079146663 hasPublicationYear "2013" @default.
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