ArticlePloS one2011
AcrB trimer stability and efflux activity, insight from mutagenesis studies.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- The Shape of Things to Come: α-Helical Membrane Protein Folding on the Ribosome.Chemical reviews · 2026Review
- Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance.Microbiology and molecular biology reviews : MMBR · 2024Review
- Structural analysis of resistance-nodulation cell division transporters.Microbiology and molecular biology reviews : MMBR · 2024Review
- Molecular insights into the determinants of substrate specificity and efflux inhibition of the RND efflux pumps AcrB and AdeB.Microbiology (Reading, England) · 2024Review
- Update on the Discovery of Efflux Pump Inhibitors against Critical Priority Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2023Review
- How physical forces drive the process of helical membrane protein folding.EMBO reports · 2022Review
- Structure and function relationship of OqxB efflux pump from Klebsiella pneumoniae.Nature communications · 2021Article
- Structure, Assembly, and Function of Tripartite Efflux and Type 1 Secretion Systems in Gram-Negative Bacteria.Chemical reviews · 2021Review
- Probing the Dynamics of AcrB Through Disulfide Bond Formation.ACS omega · 2020Article
- Native Cell Membrane Nanoparticles System for Membrane Protein-Protein Interaction Analysis.Journal of visualized experiments : JoVE · 2020Article
- Comparison of in vitro and in vivo oligomeric states of a wild type and mutant trimeric inner membrane multidrug transporter.Biochemistry and biophysics reports · 2018Article
- Nitrothiophene carboxamides, a novel narrow spectrum antibacterial series: Mechanism of action and Efficacy.Scientific reports · 2018Article
- Improving olefin tolerance and production in E. coli using native and evolved AcrB.Biotechnology and bioengineering · 2015Article
- Repressive mutations restore function-loss caused by the disruption of trimerization in Escherichia coli multidrug transporter AcrB.Frontiers in microbiology · 2015Article
- Unfolding study of a trimeric membrane protein AcrB.Protein science : a publication of the Protein Society · 2014Article
- Correlation between AcrB trimer association affinity and efflux activity.Biochemistry · 2014Article
- Assembling of AcrB trimer in cell membrane.Journal of molecular biology · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multidrug transporter AcrB in Escherichia coli exists and functions as a homo-trimer. The assembly process of obligate membrane protein oligomers, including AcrB, remains poorly understood. In a previous study, we have shown that individual AcrB subunit is capable of folding independently, suggesting that trimerization of AcrB follows a three-stage pathway in which monomers first fold, and then assemble. Here we destabilized the AcrB trimer through mutating a single Pro (P223) in the protruding loop of AcrB, which drastically reduced the protein activity. We replaced P223 separately with five residues, including Ala, Val, Tyr, Asn, and Gly, and found that AcrB(P223G) was the least active. Detailed characterization of AcrB(P223G) revealed that the protein existed as a well-folded monomer after purification, but formed a trimer in vivo. The function of the mutant could be partly restored through strengthening the stability of the trimer using an inter-subunit disulfide bond. Our results also suggested that the protruding loop is well structured during AcrB assembly with P223 served as a "wedge" close to the tip to stabilize the AcrB trimer structure. When this wedge is disrupted, the stability of the trimer is reduced, accompanied by a decrease of drug efflux activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.