title: Structural mechanisms of heavy-metal extrusion by the Cus efflux system.
abstract: Resistance-nodulation-cell division (RND) superfamily efflux systems are responsible for the active transport of toxic compounds from the Gram-negative bacterial cell. These pumps typically assemble as tripartite complexes, spanning the inner and outer membranes of the cell envelope. In Escherichia coli, the CusC(F)BA complex, which exports copper(I) and silver(I) and mediates resistance to these two metal ions, is the only known RND transporter with a specificity for heavy metals. We have determined the crystal structures of both the inner membrane pump CusA and membrane fusion protein CusB, as well as the adaptor-transporter CusBA complex formed by these two efflux proteins. In addition, the crystal structures of the outer membrane channel CusC and the periplasmic metallochaperone CusF have been resolved. Based on these structures, the entire assembled model of the tripartite efflux system has been developed, and this efflux complex should be in the form of CusC3-CusB6-CusA3. It has been shown that CusA utilizes methionine clusters to bind and export Cu(I) and Ag(I). This pump is likely to undergo a conformational change, and utilize a relay network of methionine clusters as well as conserved charged residues to extrude the metal ions from the bacterial cell.
authors: Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA.
authors: Jared A
authors: JA
authors: Delmar
authors: Chih-Chia
authors: CC
authors: Su
authors: Edward W
authors: EW
authors: Yu
mesh_terms: D001692:Biological Transport; D003300:Copper / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism; D019216:Metals, Heavy / Q000378:metabolism*; D008962:Models, Theoretical; D012834:Silver / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D019216:Metals, Heavy; D012834:Silver; D003300:Copper
references: Biochemistry. 2005 Aug 9;44(31):10533-40
references: 16060662
references: Structure. 2010 Mar 14;18(4):507-17
references: 20399187
references: Science. 2003 May 9;300(5621):976-80
references: 12738864
references: Science. 2006 Sep 1;313(5791):1295-8
references: 16946072
references: Nature. 2010 Sep 23;467(7314):484-8
references: 20865003
references: J Bacteriol. 2003 Jul;185(13):3804-12
references: 12813074
references: Nature. 2006 Sep 14;443(7108):173-9
references: 16915237
references: Nat Chem Biol. 2008 Feb;4(2):107-9
references: 18157124
references: J Am Chem Soc. 2011 Dec 7;133(48):19330-3
references: 22029374
references: Biochemistry. 2011 Apr 5;50(13):2559-66
references: 21323389
references: J Bacteriol. 2006 Oct;188(20):7290-6
references: 17015668
references: Biophys J. 2008 Dec 15;95(12):5681-91
references: 18835894
references: Nature. 2011 Nov 27;480(7378):565-9
references: 22121023
references: J Bacteriol. 2005 Mar;187(6):1923-9
references: 15743938
references: Protein Sci. 2007 Oct;16(10):2287-93
references: 17893365
references: Microbiology (Reading). 2001 Apr;147(Pt 4):965-972
references: 11283292
references: J Bacteriol. 2002 Aug;184(15):4168-76
references: 12107134
references: J Bacteriol. 2005 Oct;187(19):6804-15
references: 16166543
references: J Bacteriol. 2001 Oct;183(20):5803-12
references: 11566977
references: Nature. 2011 Feb 24;470(7335):558-62
references: 21350490
references: J Bacteriol. 2000 Mar;182(6):1754-6
references: 10692383
references: J Mol Microbiol Biotechnol. 1999 Aug;1(1):107-25
references: 10941792
references: J Bacteriol. 1993 Oct;175(19):6299-313
references: 8407802
references: J Struct Biol. 2007 Jun;158(3):494-502
references: 17275331
references: PLoS One. 2011 Jan 07;6(1):e15610
references: 21249122
references: J Bacteriol. 2006 Aug;188(16):5693-703
references: 16885437
references: J Biol Chem. 2007 Dec 7;282(49):35695-702
references: 17893146
references: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7190-5
references: 10377390
references: J Mol Biol. 2009 Oct 23;393(2):342-55
references: 19695261
references: J Bacteriol. 2005 Nov;187(22):7815-25
references: 16267305
references: Nature. 2002 Oct 10;419(6907):587-93
references: 12374972
references: J Mol Biol. 2012 Sep 21;422(3):429-41
references: 22683351
references: Structure. 2007 Dec;15(12):1663-73
references: 18073115
references: J Bacteriol. 2011 May;193(10):2381-7
references: 21398536
references: Biochemistry. 2008 Nov 4;47(44):11408-14
references: 18847219
references: J Bacteriol. 2002 Aug;184(15):4161-7
references: 12107133
references: J Antimicrob Chemother. 2007 Jun;59(6):1216-22
references: 17062614
references: PLoS Biol. 2007 Jan;5(1):e7
references: 17194213