| 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
|
