气候变化领域集成服务门户(CCPortal): New free-exchange model of EmrE transport

CCPortal

DOI	10.1073/pnas.1708671114
	New free-exchange model of EmrE transport
	Robinson A.E.; Thomas N.E.; Morrison E.A.; Balthazor B.M.; Henzler-Wildman K.A.
发表日期	2017
ISSN	0027-8424
起始页码	E10083
结束页码	E10091
卷号	114 期号:47
英文摘要	EmrE is a small multidrug resistance transporter found in Escherichia coli that confers resistance to toxic polyaromatic cations due to its proton-coupled antiport of these substrates. Here we show that EmrE breaks the rules generally deemed essential for coupled antiport. NMR spectra reveal that EmrE can simultaneously bind and cotransport proton and drug. The functional consequence of this finding is an exceptionally promiscuous transporter: not only can EmrE export diverse drug substrates, it can couple antiport of a drug to either one or two protons, performing both electrogenic and electroneutral transport of a single substrate. We present a free-exchange model for EmrE antiport that is consistent with these results and recapitulates ΔpH-driven concentrative drug uptake. Kinetic modeling suggests that free exchange by EmrE sacrifices coupling efficiency but boosts initial transport speed and drug release rate, which may facilitate efficient multidrug efflux. © 2017, National Academy of Sciences. All rights reserved.
英文关键词	Coupled transport; Membrane protein; Multidrug transport; NMR; Protein dynamics
语种	英语
scopus关键词	Escherichia coli protein; glutamic acid; multidrug resistance protein; multidrug transporter EmrE; unclassified drug; 1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; 1-palmitoyl-2-oleoylphosphatidylcholine; antiporter; cation; dicyclohexylcarbodiimide; EmrE protein, E coli; Escherichia coli protein; organophosphorus compound; phosphatidylcholine; phosphatidylglycerol; protein binding; proteolipid; proteoliposomes; proton; recombinant protein; tetraphenylphosphonium; xenobiotic agent; Article; conformational transition; controlled study; drug binding site; drug uptake; Escherichia coli; flux assay; hydrophobicity; isothermal titration calorimetry; kinetics; membrane potential; nonhuman; nuclear magnetic resonance spectroscopy; priority journal; proton motive force; proton transport; stoichiometry; binding site; chemistry; drug effect; enzyme specificity; Escherichia coli; gene expression; genetics; metabolism; molecular dynamics; multidrug resistance; pH; protein domain; protein secondary structure; thermodynamics; transport at the cellular level; Antiporters; Binding Sites; Biological Transport; Dicyclohexylcarbodiimide; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Proteins; Gene Expression; Hydrogen-Ion Concentration; Kinetics; Molecular Dynamics Simulation; Onium Compounds; Organophosphorus Compounds; Phosphatidylcholines; Phosphatidylglycerols; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Secondary; Proteolipids; Protons; Recombinant Proteins; Substrate Specificity; Thermodynamics; Xenobiotics
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160575
作者单位	Robinson, A.E., Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States, Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States; Thomas, N.E., Department of Biochemistry, University of Wisconsin at Madison, Madison, WI 53706, United States; Morrison, E.A., Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States, Department of Biochemistry, University of Iowa Carver College of Med icine, Iowa City, IA 52242, United States; Balthazor, B.M., Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, United States, Biotherapeutics Pharmaceutical Sciences Research and Development Pfizer Inc., Chesterfield, MO 63017, United States; Henzler-Wildman, K.A., Department ...
推荐引用方式 GB/T 7714	Robinson A.E.,Thomas N.E.,Morrison E.A.,et al. New free-exchange model of EmrE transport[J],2017,114(47).
APA	Robinson A.E.,Thomas N.E.,Morrison E.A.,Balthazor B.M.,&Henzler-Wildman K.A..(2017).New free-exchange model of EmrE transport.Proceedings of the National Academy of Sciences of the United States of America,114(47).
MLA	Robinson A.E.,et al."New free-exchange model of EmrE transport".Proceedings of the National Academy of Sciences of the United States of America 114.47(2017).