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| | ==Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump-MacB section== | | ==Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump-MacB section== |
| - | <StructureSection load='5nil' size='340' side='right' caption='[[5nil]], [[Resolution|resolution]] 5.30Å' scene=''> | + | <SX load='5nil' size='340' side='right' viewer='molstar' caption='[[5nil]], [[Resolution|resolution]] 5.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5nil]] is a 11 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NIL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NIL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5nil]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NIL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NIL FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5nil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nil OCA], [http://pdbe.org/5nil PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nil RCSB], [http://www.ebi.ac.uk/pdbsum/5nil PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nil ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 5.3Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5nil FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nil OCA], [https://pdbe.org/5nil PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nil RCSB], [https://www.ebi.ac.uk/pdbsum/5nil PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nil ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TOLC_ECOLI TOLC_ECOLI]] Outer membrane channel, which is required for the function of several efflux systems such as AcrAB-TolC, AcrEF-TolC, EmrAB-TolC and MacAB-TolC. These systems are involved in export of antibiotics and other toxic compounds from the cell. TolC is also involved in import of colicin E1 into the cells.<ref>PMID:6337123</ref> <ref>PMID:11274125</ref> <ref>PMID:15228545</ref> <ref>PMID:18955484</ref> <ref>PMID:23176499</ref> [[http://www.uniprot.org/uniprot/MACB_ECOLI MACB_ECOLI]] Part of the tripartite efflux system MacAB-TolC. MacB is a non-canonical ABC transporter that contains transmembrane domains (TMD), which form a pore in the inner membrane, and an ATP-binding domain (NBD), which is responsible for energy generation. When overexpressed, the system confers resistance against macrolides composed of 14- and 15-membered lactones but no or weak resistance against 16-membered ones. In addition, the system could also transport R-LPS or a similar glycolipid.<ref>PMID:11544226</ref> <ref>PMID:17214741</ref> <ref>PMID:18955484</ref> <ref>PMID:23974027</ref> [[http://www.uniprot.org/uniprot/MACA_ECOLI MACA_ECOLI]] Part of the tripartite efflux system MacAB-TolC. MacA stimulates the ATPase activity of MacB by promoting the closed ATP-bound state of MacB, increases the capacity of MacB to bind macrolides such as erythromycin, and provides a physical link between MacB and TolC. When overexpressed, the system confers resistance against macrolides composed of 14- and 15-membered lactones but no or weak resistance against 16-membered ones. In addition, MacA binds tightly rough-core lipopolysaccharide (R-LPS), suggesting that the system could also transport R-LPS or a similar glycolipid.<ref>PMID:11544226</ref> <ref>PMID:17214741</ref> <ref>PMID:18955484</ref> <ref>PMID:21696464</ref> <ref>PMID:23974027</ref> | + | [https://www.uniprot.org/uniprot/TOLC_ECOLI TOLC_ECOLI] Outer membrane channel, which is required for the function of several efflux systems such as AcrAB-TolC, AcrEF-TolC, EmrAB-TolC and MacAB-TolC. These systems are involved in export of antibiotics and other toxic compounds from the cell. TolC is also involved in import of colicin E1 into the cells.<ref>PMID:6337123</ref> <ref>PMID:11274125</ref> <ref>PMID:15228545</ref> <ref>PMID:18955484</ref> <ref>PMID:23176499</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| - | [[Category: Bai, X C]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Blaza, J N]] | + | [[Category: Large Structures]] |
| - | [[Category: Du, D]] | + | [[Category: Bai X-C]] |
| - | [[Category: Fitzpatrick, A W.P]] | + | [[Category: Blaza JN]] |
| - | [[Category: Llabres, S]] | + | [[Category: Du D]] |
| - | [[Category: Luisi, B F]] | + | [[Category: Fitzpatrick AWP]] |
| - | [[Category: Murakami, S]] | + | [[Category: Llabres S]] |
| - | [[Category: Neuberger, A]] | + | [[Category: Luisi BF]] |
| - | [[Category: Okada, U]] | + | [[Category: Murakami S]] |
| - | [[Category: Scheres, S H.W]] | + | [[Category: Neuberger A]] |
| - | [[Category: Veen, H W.van]]
| + | [[Category: Okada U]] |
| - | [[Category: Zachariae, U]] | + | [[Category: Scheres SHW]] |
| - | [[Category: Abc transporter]] | + | [[Category: Zachariae U]] |
| - | [[Category: Drug efflux pump]]
| + | [[Category: Van Veen HW]] |
| - | [[Category: Macrolide transporter]]
| + | |
| - | [[Category: Multi-drug resistance]]
| + | |
| - | [[Category: Toxin transporter]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
TOLC_ECOLI Outer membrane channel, which is required for the function of several efflux systems such as AcrAB-TolC, AcrEF-TolC, EmrAB-TolC and MacAB-TolC. These systems are involved in export of antibiotics and other toxic compounds from the cell. TolC is also involved in import of colicin E1 into the cells.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The MacA-MacB-TolC assembly of Escherichia coli is a transmembrane machine that spans the cell envelope and actively extrudes substrates, including macrolide antibiotics and polypeptide virulence factors. These transport processes are energized by the ATPase MacB, a member of the ATP-binding cassette (ABC) superfamily. We present an electron cryo-microscopy structure of the ABC-type tripartite assembly at near-atomic resolution. A hexamer of the periplasmic protein MacA bridges between a TolC trimer in the outer membrane and a MacB dimer in the inner membrane, generating a quaternary structure with a central channel for substrate translocation. A gating ring found in MacA is proposed to act as a one-way valve in substrate transport. The MacB structure features an atypical transmembrane domain with a closely packed dimer interface and a periplasmic opening that is the likely portal for substrate entry from the periplasm, with subsequent displacement through an allosteric transport mechanism.
Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump.,Fitzpatrick AWP, Llabres S, Neuberger A, Blaza JN, Bai XC, Okada U, Murakami S, van Veen HW, Zachariae U, Scheres SHW, Luisi BF, Du D Nat Microbiol. 2017 May 15;2:17070. doi: 10.1038/nmicrobiol.2017.70. PMID:28504659[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Morona R, Manning PA, Reeves P. Identification and characterization of the TolC protein, an outer membrane protein from Escherichia coli. J Bacteriol. 1983 Feb;153(2):693-9. PMID:6337123
- ↑ Kobayashi K, Tsukagoshi N, Aono R. Suppression of hypersensitivity of Escherichia coli acrB mutant to organic solvents by integrational activation of the acrEF operon with the IS1 or IS2 element. J Bacteriol. 2001 Apr;183(8):2646-53. PMID:11274125 doi:http://dx.doi.org/10.1128/JB.183.8.2646-2653.2001
- ↑ Touze T, Eswaran J, Bokma E, Koronakis E, Hughes C, Koronakis V. Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system. Mol Microbiol. 2004 Jul;53(2):697-706. PMID:15228545 doi:http://dx.doi.org/10.1111/j.1365-2958.2004.04158.x
- ↑ Lin HT, Bavro VN, Barrera NP, Frankish HM, Velamakanni S, van Veen HW, Robinson CV, Borges-Walmsley MI, Walmsley AR. MacB ABC transporter is a dimer whose ATPase activity and macrolide-binding capacity are regulated by the membrane fusion protein MacA. J Biol Chem. 2009 Jan 9;284(2):1145-54. doi: 10.1074/jbc.M806964200. Epub 2008, Oct 27. PMID:18955484 doi:http://dx.doi.org/10.1074/jbc.M806964200
- ↑ Zakharov SD, Sharma O, Zhalnina M, Yamashita E, Cramer WA. Pathways of colicin import: utilization of BtuB, OmpF porin and the TolC drug-export protein. Biochem Soc Trans. 2012 Dec 1;40(6):1463-8. doi: 10.1042/BST20120211. PMID:23176499 doi:http://dx.doi.org/10.1042/BST20120211
- ↑ Fitzpatrick AWP, Llabres S, Neuberger A, Blaza JN, Bai XC, Okada U, Murakami S, van Veen HW, Zachariae U, Scheres SHW, Luisi BF, Du D. Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump. Nat Microbiol. 2017 May 15;2:17070. doi: 10.1038/nmicrobiol.2017.70. PMID:28504659 doi:http://dx.doi.org/10.1038/nmicrobiol.2017.70
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