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Escherichia coli K-12 substr. MG1655 Transporter: AcrAB-TolC multidrug efflux system

Subunit composition of AcrAB-TolC multidrug efflux system = [AcrA]6[(TolC)3][AcrB]3
         AcrAB-TolC multidrug efflux system - membrane fusion protein = AcrA (extended summary available)
         TolC outer membrane channel = (TolC)3 (extended summary available)
                 TolC monomer = TolC
         AcrAB-TolC multidrug efflux system - permease subunit = AcrB (extended summary available)

Summary:
AcrAB and TolC make up a three-component proton motive force-dependent multidrug efflux system which confers resistance to multiple antimicrobial agents. The complex is the major contributor to the intrinsic resistance of E. coli to organic solvents [Tsukagoshi00], dyes and detergents as well as lipophilic antibiotics including novobiocin, erythromycin, fusidic acid and cloxacillin. The AcrAB-TolC system is a significant contributor to the intrinsic resistance of E. coli to bile acids [Thanassi97].The AcrAB-TolC complex confers only weak reistance to anionic β-lactams (aztreonam, carbenicillin, sulbenicillin) [Nishino03].The acrAB locus encodes for two of the complex proteins, AcrA and AcrB. AcrA is a periplasmic lipoprotein component which is a member of the membrane fusion protein (MFP) family and is anchored to the inner membrane's outer surface by its lipid moiety. AcrB is an RND-type inner-membrane associated efflux pump. Reconstitution studies suggest that AcrB is a proton-substrate antiporter [Zgurskaya99]. The crystal structure of the AcrB trimer reveals an asymmetric assembly of the monomers and suggests a functionally rotating, three step (access, binding, and extrusion), peristaltic pump mechanism for the export of substrates [Seeger06, Murakami06, Pos09]. The small membrane protein AcrZ associates with AcrAB-TolC and may affect the specificity of drug export [Hobbs12].

AcrABTolC provides minimal reistance to ethidium and acriflavine in an emrE mdfA double null background [Tal09] suggesting that tripartite pumps may act cooperatively with single component major facilitator superfamily (MFS) and small multidrug resistance (SMR) transporters to export hydrophobic drugs/toxins from the cytoplasm in a two step process [Lee00a, Tal09].

Expression of the complex is constitutive and does not require the presence of substrate [Touze04]. Overexpression of the complex components results in significant levels of resistance to other common antibiotics such as tetracycline and chloramphenicol [Okusu96].

AcrA and AcrB were found as homotrimers within the inner membrane and assemble with trimeric TolC to form the efflux pump [Stenberg05]. Genetic, cross-linking, and protein purification studies suggest that the TolC channel associates with AcrAB to form a tri-partite complex spanning the entire cell envelope [Fralick96, Gerken04, Tikhonova04, Touze04]. Cross-linking studies [Zgurskaya00] suggest that AcrA interacts with AcrB as an oligomeric trimer or dimer and that the AcrA/AcrB complex can exist in a stable state associated with the inner membrane independently of the TolC outer membrane channel. A small region of AcrA located near its C-terminus has been shown to be necessary for interaction with AcrB [Elkins03]. Cross-linking and titration calorimetry studies reveal interaction between AcrB and AcrA as well as interaction between AcrA and TolC, suggesting a role for AcrA as an adaptor between AcrB and TolC [Touze04, Husain04]. Interaction between AcrA and TolC is important for export [Stegmeier06]. Cross-linking studies have also suggested a direct interaction between TolC and AcrB [Touze04, Tamura05].

The structure of E.coli AcrA has been modelled on the basis of crystallographic data from Pseudomonas aeruginosa [Higgins04a, Symmons09]. The intermolecular contacts between AcrA and AcrB have been mapped using an in vivo cross-linking approach and the AcrAB complex has been modelled [Symmons09]. A complete assembly of the AcrAB-TolC complex has been modelled [Symmons09].

Fusion proteins of AcrA-AcrB, AcrA-AcraZ and TolC remain associated during purification and the purified complex retains partial activity. A pseudo-atomic model of the complex has been constructed which comprises an AcrB trimer, an AcrA hexamer and TolC trimer. In the model no direct interaction between AcrB and TolC is observed, rather AcrA acts as a bridge between them [Du14].

Review: [Eicher09]

Citations: [Xu11a, Kobayashi14]

Gene-Reaction Schematic: ?

Credits:
Last-Curated ? 30-Jun-2009 by Mackie A , Macquarie University


Enzymatic reaction of: multidrug efflux transporter (AcrAB-TolC multidrug efflux system)

Summary:
Kinetic behaviour of the complex has been investigated for various cephalosporins [Nagano09].
Nitrocefin Km: 5 μM
Cephalothin Km: 91.2 μM
Cefamandole Km: 19.6 μM
Cephaloridine Km: 288 μM
The latter three compounds showed strong positive cooperativity with Hill coefficients of 1.9, 3.2 and 1.75 respectively.

Please note: AcrABTolC exports substrates from the periplasm and from the cytoplasm according to the following reactions:
drug(periplasmic space) + H+(periplasmic space) ===> drug(extracellular) + H+(cytoplasm)

drug(cytoplasm) + H+(periplasmic space) ===> drug(extracellular) + H+(cytoplasm)


Enzymatic reaction of: chenodeoxycholate efflux (AcrAB-TolC multidrug efflux system)


Subunit of AcrAB-TolC multidrug efflux system: AcrAB-TolC multidrug efflux system - membrane fusion protein

Synonyms: SipB, Mbl, Lir, NbsA, MtcA, AcrA, acridine efflux pump, AcrA membrane fusion protein

Gene: acrA Accession Numbers: EG11703 (EcoCyc), b0463, ECK0457

Locations: periplasmic space, inner membrane

Sequence Length: 397 AAs

Molecular Weight: 42.197 kD (from nucleotide sequence)

GO Terms:

Biological Process: GO:0006855 - drug transmembrane transport Inferred from experiment [Okusu96]
GO:0015721 - bile acid and bile salt transport Inferred from experiment [Thanassi97]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11]
GO:0046677 - response to antibiotic Inferred by computational analysis [UniProtGOA11]
GO:0055085 - transmembrane transport Inferred by computational analysis [GOA01a]
Molecular Function: GO:0015238 - drug transmembrane transporter activity Inferred from experiment [Ma93a]
GO:0042802 - identical protein binding Inferred from experiment [Rajagopala14, Yum09, Stenberg05]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, Stenberg05]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11, GOA01a]
GO:0030288 - outer membrane-bounded periplasmic space

MultiFun Terms: cell processes protection drug resistance/sensitivity
cell structure membrane
transport Electrochemical potential driven transporters Porters (Uni-, Sym- and Antiporters)

Unification Links: DIP:DIP-29039N , EcoliWiki:b0463 , ModBase:P0AE06 , PR:PRO_000022048 , Pride:P0AE06 , Protein Model Portal:P0AE06 , RefSeq:NP_414996 , SMR:P0AE06 , String:511145.b0463 , Swiss-Model:P0AE06 , UniProt:P0AE06

Relationship Links: InterPro:IN-FAMILY:IPR006143 , PDB:Structure:2F1M , Pfam:IN-FAMILY:PF00529 , Prosite:IN-FAMILY:PS51257

Summary:
AcrA is the periplasmic lipoprotein component of the AcrAB-TolC multidrug efflux pump in Escherichia coli and can function in chimeric constructions with three other RND-family pumps, AcrD, AcrF and MdtF(YhiV). The C-terminal domain of AcrA is functionally significant [Ge09a] and a small region located near the C-terminus has been shown to be necessary for interaction with AcrB [Elkins03]. A stable fragment of AcrA has been crystallized and its three-dimensional structure determined [Mikolosko06].

The structure of E.coli AcrA has been modelled on the basis of crystallographic data from Pseudomonas aeruginosa [Higgins04a, Symmons09]. The intermolecular contacts between AcrA and AcrB have been mapped using an in vivo cross-linking approach and the AcrAB complex has been modelled [Symmons09].

acrA is one of a network of genes believed to play a role in promoting the stress-induced mutagenesis (SIM) response of E. coli K-12 [Al12].

Essentiality data for acrA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Subunit of AcrAB-TolC multidrug efflux system: TolC outer membrane channel

Synonyms: weeA, colE1-i, mtcB, mukA, refI, toc

Gene: tolC Accession Numbers: EG11009 (EcoCyc), b3035, ECK3026

Locations: outer membrane

Subunit composition of TolC outer membrane channel = [TolC]3
         TolC monomer = TolC

Map Position: [3,176,137 -> 3,177,618] (68.46 centisomes)
Length: 1482 bp / 493 aa

Molecular Weight of Polypeptide: 53.741 kD (from nucleotide sequence)

GO Terms:

Biological Process: GO:0014070 - response to organic cyclic compound Inferred from experiment [Aono98]
GO:0042930 - enterobactin transport Inferred from experiment [Bleuel05]
GO:0055085 - transmembrane transport Inferred from experiment [Benz93, Wandersman90]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11, GOA01a]
GO:0015031 - protein transport Inferred by computational analysis [GOA01a]
GO:0046677 - response to antibiotic Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0015288 - porin activity Inferred from experiment [Benz93]
GO:0015562 - efflux transmembrane transporter activity Inferred from experiment [Wandersman90]
GO:0005215 - transporter activity Inferred by computational analysis [GOA01a]
Cellular Component: GO:0009279 - cell outer membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, DiazMejia09, Han12a, Zhang07, Molloy00, LopezCampistrou05, Morona83]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11]
GO:0019867 - outer membrane Inferred by computational analysis [GOA01a]

MultiFun Terms: cell processes cell division
transport Channel-type Transporters Beta barrel porins (The Outer Membrane Porin (OMP) Functional Superfamily)

Unification Links: DIP:DIP-11007N , EcoliWiki:b3035 , ModBase:P02930 , PR:PRO_000024080 , Protein Model Portal:P02930 , RefSeq:NP_417507 , SMR:P02930 , String:511145.b3035 , UniProt:P02930

Relationship Links: InterPro:IN-FAMILY:IPR003423 , InterPro:IN-FAMILY:IPR010130 , PDB:Structure:1EK9 , PDB:Structure:1TQQ , PDB:Structure:2VDD , PDB:Structure:2VDE , PDB:Structure:2WMZ , PDB:Structure:2XMN , Pfam:IN-FAMILY:PF02321

Summary:
TolC is an outer membrane porin involved in the efflux of several hydrophobic and amphipathic molecules. TolC functions as a trimer and is a common outer membrane component of several multi-drug efflux systems.

The tolC gene product localises to the outer membrane [Morona83]. TolC was purified from the Escherichia coli outer membrane as a trimer and its structure was determined by two dimensional projection at a resolution of 12 Å. TolC was found to be an outer membrane protein with each monomer comprising a membrane domain, predicted to be beta-barrel, and a C-terminal periplasmic domain [Koronakis97]. Targeting of TolC to the Sec-translocase for transport across the inner membrane is SecB-dependent [Baars06]. The three dimensional crystal structure of TolC has been determined in an unbound state to a 2.1 Å resolution and in a ligand-bound complex to a 2.75 Å resolution. Each protomer of TolC contributes four β strands to the outer membrane β-barrel structure and four alpha helices to a contiguous α-helical barrel that extends into the periplasm [Koronakis00, Higgins04].

Reconstitution studies suggest that TolC is an outer membrane channel for peptides [Benz93]. TolC is required for the function of the AcrAB multidrug efflux system [Fralick96] and its homologs AcrEF [Kobayashi01a] and YhiUV [Nishino02], the EmrAB drug efflux system [BorgesWalmsley03], the EmrAB homolog, EmrKY [Tanabe97], the MdtABC drug efflux system [Nagakubo02] and the MacAB macrolide extrusion system [Kobayashi01b]. Crystal structures of TolC mutants reveal partially open states of the porin and indicate regions which appear to be involved in binding the periplasmic component of ArcAB [Bavro08].

The mutant phenotype from growth assays suggest TolC is involved in export of thymine when thymidine is the sole carbon source, though an inner membrane export system has not yet been identified [Reed06].

Gene expression analyses indicate that tolC is essential for L-cysteine tolerance and that tolC overexpression is effective for L-cysteine production in E. coli cells [Wiriyathanawudh09].

Mutations in tolC result in a reduction in the synthesis of OmpF porin and an increase in the level of OmpC porin synthesis [Misra87]. Down regulation of tolC is observed under starvation conditions [Muela08]. TolC deficient E.coli cells show decreased growth rates and altered morphology when grown in glucose minimal media. This phenotype is exacerbated by lack of ybiBC and/or yjfMC [Dhamdhere10]. ΔtolC cells are morphologically abnormal - they are often longer and exhibit coccoid shaped bulges. The observed growth impairment and abnormal morhology can be complemented by tolC expressed in trans, by the addition of iron to the culture medium or by deleting any of the genes involved in enterobactin synthesis (entC, entA, entB, entE or entF). The morphological defects and growth impairment of ΔtolC cells grown in glucose minimal medium are due to the accumulation of enterobactin in the periplasm of E. coli K-12 [Vega13].

Reviews: [Koronakis04, Zgurskaya11]

Citations: [Vaccaro08, Lin08a, Zhang08b]

Essentiality data for tolC knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Subunit of AcrAB-TolC multidrug efflux system: AcrAB-TolC multidrug efflux system - permease subunit

Synonyms: AcrE, AcrB, AcrB RND permease

Gene: acrB Accession Numbers: EG11704 (EcoCyc), b0462, ECK0456

Locations: inner membrane

Sequence Length: 1049 AAs

Molecular Weight: 113.57 kD (from nucleotide sequence)

GO Terms:

Biological Process: GO:0006855 - drug transmembrane transport Inferred from experiment [Okusu96]
GO:0042493 - response to drug Inferred from experiment [Ma93a]
GO:0046618 - drug export Inferred from experiment [Zgurskaya99]
GO:0006810 - transport Inferred by computational analysis [UniProtGOA11, GOA01a]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Hobbs12]
GO:0015238 - drug transmembrane transporter activity Inferred from experiment [Ma93a]
GO:0015307 - drug:proton antiporter activity Inferred from experiment [Zgurskaya99]
GO:0005215 - transporter activity Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, DiazMejia09, Zhang07, Daley05]
GO:0005887 - integral component of plasma membrane Inferred from experiment Inferred by computational analysis [Ma93a]
GO:0016020 - membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01a, Lasserre06]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11, GOA01a]

MultiFun Terms: cell processes protection drug resistance/sensitivity
cell structure membrane
transport Electrochemical potential driven transporters Porters (Uni-, Sym- and Antiporters)

Unification Links: DIP:DIP-9049N , EcoliWiki:b0462 , Mint:MINT-1286285 , ModBase:P31224 , PR:PRO_000022049 , Pride:P31224 , Protein Model Portal:P31224 , RefSeq:NP_414995 , SMR:P31224 , String:511145.b0462 , UniProt:P31224

Relationship Links: InterPro:IN-FAMILY:IPR001036 , InterPro:IN-FAMILY:IPR004764 , InterPro:IN-FAMILY:IPR027463 , PDB:Structure:1IWG , PDB:Structure:1OY6 , PDB:Structure:1OY8 , PDB:Structure:1OY9 , PDB:Structure:1OYD , PDB:Structure:1OYE , PDB:Structure:1T9T , PDB:Structure:1T9U , PDB:Structure:1T9V , PDB:Structure:1T9W , PDB:Structure:1T9X , PDB:Structure:1T9Y , PDB:Structure:2DHH , PDB:Structure:2DR6 , PDB:Structure:2DRD , PDB:Structure:2GIF , PDB:Structure:2HQC , PDB:Structure:2HQD , PDB:Structure:2HQF , PDB:Structure:2HQG , PDB:Structure:2HRT , PDB:Structure:2I6W , PDB:Structure:2J8S , PDB:Structure:2RDD , PDB:Structure:2W1B , PDB:Structure:3AOA , PDB:Structure:3AOB , PDB:Structure:3AOC , PDB:Structure:3AOD , PDB:Structure:3D9B , PDB:Structure:3NOC , PDB:Structure:3NOG , PDB:Structure:3W9H , PDB:Structure:4DX5 , PDB:Structure:4DX6 , PDB:Structure:4DX7 , PDB:Structure:4K7Q , Pfam:IN-FAMILY:PF00873 , Prints:IN-FAMILY:PR00702

Summary:
AcrB is an RND-type inner-membrane associated proton-substrate antiporter. It functions as a part of the AcrAB/TolC multidrug-efflux complex, linking electrochemical-gradient energy to drug efflux.

The crystal structure of AcrB has been determined at 3.5 [Murakami02], 2.9, 3.0 [Seeger06], and 2.8 Å resolution [Murakami06]. Crystal structures of AcrB with bound ligands rhodamine 6G, ethidium, dequalinium, and ciprofloxacin [Yu03b, Yu03c] and with with deoxycholate (bile acid) [Drew08] have been reported. The crystal structure of AcrB in complex with a designed protein that binds and inhibits the pump has been determined at 2.5 Å resolution [Sennhauser07]. The AcrB monomer contains 12 transmembrane (TM) α helices and two large periplasmic loops - one between TM1 and 2, the other between TM7 and 8. The AcrB monomers form a trimer and a functionally rotating, three step (access, binding, and extrusion), peristaltic pump mechanism for the export of substrates [Seeger06, Murakami06, Sennhauser07, Pos09, Eicher12] has been proposed. Inactivation of any one of the three protomeric units of the trimer inactivates the entire complex [Takatsuka09].

Substrate molecules are captured by AcrB from the periplasm or the periplasm/inner membrane interface [Elkins02, Husain10]. Vestibules (openings between protomers) which are located just outside the external surface of the membrane bilayer may be important for substrate entry [Murakami02, Husain11]. AcrB has two multisite drug binding pockets that line the drug translocation channel [Nakashima11].

The crystal structure of AcrB bound by a pyridpyrimidine derived inhibitor has been determined. The inhibitor binds tightly to a hydrophobic 'trap' that is located off the substrate translocation channel and inhibits functional rotation of the AcrB monomer [Nakashima13].

The intermolecular contacts between AcrB and the periplasmic adaptor protein AcrA have been mapped using an in vivo cross-linking approach and the AcrAB complex has been modelled [Symmons09].

Site-directed mutagenesis experiments have identified amino acid residues of funtional importance in AcrB [Bohnert08, Seeger09] and in addition residues that confer macrolide resistance [Wehmeier08].

AcrB may play a role in contact dependent growth inhibition. This activity can be separated from its function as part of the AcrAB/TolC multidrug efflux complex [Aoki08]

acrB is one of a network of genes believed to play a role in promoting the stress-induced mutagenesis (SIM) response of E. coli K-12 [Al12].

acrB: acriflavine resistance protein B.

Reviews: [Seeger08, Elkins03a, Eicher09, Murakami08, Nikaido09].
Comment: [Schuldiner06]

Citations: [Takatsuka07, Fang12, Yu11a, Zgurskaya09, Lu14a]

Essentiality data for acrB knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

References

Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Aoki08: Aoki SK, Malinverni JC, Jacoby K, Thomas B, Pamma R, Trinh BN, Remers S, Webb J, Braaten BA, Silhavy TJ, Low DA (2008). "Contact-dependent growth inhibition requires the essential outer membrane protein BamA (YaeT) as the receptor and the inner membrane transport protein AcrB." Mol Microbiol 70(2);323-40. PMID: 18761695

Aono98: Aono R, Tsukagoshi N, Yamamoto M (1998). "Involvement of outer membrane protein TolC, a possible member of the mar-sox regulon, in maintenance and improvement of organic solvent tolerance of Escherichia coli K-12." J Bacteriol 180(4);938-44. PMID: 9473050

Baars06: Baars L, Ytterberg AJ, Drew D, Wagner S, Thilo C, van Wijk KJ, de Gier JW (2006). "Defining the role of the Escherichia coli chaperone SecB using comparative proteomics." J Biol Chem 281(15);10024-34. PMID: 16352602

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bavro08: Bavro VN, Pietras Z, Furnham N, Perez-Cano L, Fernandez-Recio J, Pei XY, Misra R, Luisi B (2008). "Assembly and channel opening in a bacterial drug efflux machine." Mol Cell 30(1);114-21. PMID: 18406332

Benz93: Benz R, Maier E, Gentschev I (1993). "TolC of Escherichia coli functions as an outer membrane channel." Zentralbl Bakteriol 278(2-3);187-96. PMID: 7688606

Bleuel05: Bleuel C, Grosse C, Taudte N, Scherer J, Wesenberg D, Krauss GJ, Nies DH, Grass G (2005). "TolC is involved in enterobactin efflux across the outer membrane of Escherichia coli." J Bacteriol 187(19);6701-7. PMID: 16166532

Bohnert08: Bohnert JA, Schuster S, Seeger MA, Fahnrich E, Pos KM, Kern WV (2008). "Site-Directed Mutagenesis Reveals Putative Substrate Binding Residues in the Escherichia coli RND Efflux Pump AcrB." J Bacteriol 190(24);8225-9. PMID: 18849422

BorgesWalmsley03: Borges-Walmsley MI, Beauchamp J, Kelly SM, Jumel K, Candlish D, Harding SE, Price NC, Walmsley AR (2003). "Identification of oligomerization and drug-binding domains of the membrane fusion protein EmrA." J Biol Chem 278(15);12903-12. PMID: 12482849

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

Dhamdhere10: Dhamdhere G, Zgurskaya HI (2010). "Metabolic shutdown in Escherichia coli cells lacking the outer membrane channel TolC." Mol Microbiol 77(3);743-54. PMID: 20545840

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Drew08: Drew D, Klepsch MM, Newstead S, Flaig R, De Gier JW, Iwata S, Beis K (2008). "The structure of the efflux pump AcrB in complex with bile acid." Mol Membr Biol 25(8);677-82. PMID: 19023693

Du14: Du D, Wang Z, James NR, Voss JE, Klimont E, Ohene-Agyei T, Venter H, Chiu W, Luisi BF (2014). "Structure of the AcrAB-TolC multidrug efflux pump." Nature. PMID: 24747401

Eicher09: Eicher T, Brandstatter L, Pos KM (2009). "Structural and functional aspects of the multidrug efflux pump AcrB." Biol Chem 390(8);693-9. PMID: 19453279

Eicher12: Eicher T, Cha HJ, Seeger MA, Brandstatter L, El-Delik J, Bohnert JA, Kern WV, Verrey F, Grutter MG, Diederichs K, Pos KM (2012). "Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop." Proc Natl Acad Sci U S A 109(15);5687-92. PMID: 22451937

Elkins02: Elkins CA, Nikaido H (2002). "Substrate specificity of the RND-type multidrug efflux pumps AcrB and AcrD of Escherichia coli is determined predominantly by two large periplasmic loops." J Bacteriol 184(23);6490-8. PMID: 12426336

Elkins03: Elkins CA, Nikaido H (2003). "Chimeric analysis of AcrA function reveals the importance of its C-terminal domain in its interaction with the AcrB multidrug efflux pump." J Bacteriol 185(18);5349-56. PMID: 12949086

Elkins03a: Elkins CA, Nikaido H (2003). "3D structure of AcrB: the archetypal multidrug efflux transporter of Escherichia coli likely captures substrates from periplasm." Drug Resist Updat 6(1);9-13. PMID: 12654283

Fang12: Fang J, Yu L, Wu M, Wei Y (2012). "Dissecting the function of a protruding loop in AcrB trimerization." J Biomol Struct Dyn. PMID: 22877148

Fralick96: Fralick JA (1996). "Evidence that TolC is required for functioning of the Mar/AcrAB efflux pump of Escherichia coli." J Bacteriol 1996;178(19);5803-5. PMID: 8824631

Ge09a: Ge Q, Yamada Y, Zgurskaya H (2009). "The C-terminal domain of AcrA is essential for the assembly and function of the multidrug efflux pump AcrAB-TolC." J Bacteriol 191(13);4365-71. PMID: 19411330

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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