title: Crystal structure of the Campylobacter jejuni CmeC outer membrane channel.
abstract: As one of the world's most prevalent enteric pathogens, Campylobacter jejuni is a major causative agent of human enterocolitis and is responsible for more than 400 million cases of diarrhea each year. The impact of this pathogen on children is of particular significance. Campylobacter has developed resistance to many antimicrobial agents via multidrug efflux machinery. The CmeABC tripartite multidrug efflux pump, belonging to the resistance-nodulation-cell division (RND) superfamily, plays a major role in drug resistant phenotypes of C. jejuni. This efflux complex spans the entire cell envelop of C. jejuni and mediates resistance to various antibiotics and toxic compounds. We here report the crystal structure of C. jejuni CmeC, the outer membrane component of the CmeABC tripartite multidrug efflux system. The structure reveals a possible mechanism for substrate export.
authors.affiliation: Department of Physics and Astronomy, Iowa State University, Ames, Iowa, 50011.
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Su
authors.forename: Abhijith
authors.initials: A
authors.lastname: Radhakrishnan
authors.forename: Nitin
authors.initials: N
authors.lastname: Kumar
authors.forename: Feng
authors.initials: F
authors.lastname: Long
authors.forename: Jani Reddy
authors.initials: JR
authors.lastname: Bolla
authors.forename: Hsiang-Ting
authors.initials: HT
authors.lastname: Lei
authors.forename: Jared A
authors.initials: JA
authors.lastname: Delmar
authors.forename: Sylvia V
authors.initials: SV
authors.lastname: Do
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Chou
authors.forename: Kanagalaghatta R
authors.initials: KR
authors.lastname: Rajashankar
authors.forename: Qijing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Edward W
authors.initials: EW
authors.lastname: Yu
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D016123:Campylobacter jejuni / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; D007473:Ion Channels; D003545:Cysteine
keywords: Campylobacter jejuni; efflux channel; membrane protein; multidrug resistance; resistance-nodulation-cell division
references.citation: J Bacteriol. 2005 Oct;187(19):6804-15
references.pmid: 16166543
references.citation: Emerg Infect Dis. 2001 Jan-Feb;7(1):24-34
references.pmid: 11266291
references.citation: Science. 2003 May 9;300(5621):976-80
references.pmid: 12738864
references.citation: Science. 2006 Sep 1;313(5791):1295-8
references.pmid: 16946072
references.citation: Clin Infect Dis. 2007 Mar 1;44(5):701-3
references.pmid: 17278063
references.citation: Antimicrob Agents Chemother. 2003 Jan;47(1):390-4
references.pmid: 12499221
references.citation: Mol Microbiol. 2013 May;88(3):590-602
references.pmid: 23565750
references.citation: Antimicrob Agents Chemother. 2005 Aug;49(8):3347-54
references.pmid: 16048946
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
references.pmid: 15572765
references.citation: Structure. 2006 Mar;14(3):577-87
references.pmid: 16531241
references.citation: Lancet Neurol. 2008 Oct;7(10):939-50
references.pmid: 18848313
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):9994-9
references.pmid: 15226509
references.citation: Nature. 2000 Jun 22;405(6789):914-9
references.pmid: 10879525
references.citation: J Biol Chem. 2004 Dec 17;279(51):52816-9
references.pmid: 15507433
references.citation: J Antimicrob Chemother. 2006 Aug;58(2):243-55
references.pmid: 16735431
references.citation: Clin Microbiol Rev. 2006 Apr;19(2):382-402
references.pmid: 16614254
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Dec;57(Pt 12):1755-62
references.pmid: 11717487
references.citation: Future Microbiol. 2009 Mar;4(2):189-200
references.pmid: 19257846
references.citation: Nature. 2000 Feb 10;403(6770):665-8
references.pmid: 10688204
references.citation: Infect Immun. 2003 Aug;71(8):4250-9
references.pmid: 12874300
references.citation: J Mol Microbiol Biotechnol. 1999 Aug;1(1):107-25
references.pmid: 10941792
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7173-8
references.pmid: 19342493
references.citation: J Antimicrob Chemother. 2006 Dec;58(6):1154-9
references.pmid: 17023497
references.citation: PLoS One. 2011 Jan 07;6(1):e15610
references.pmid: 21249122
references.citation: Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
references.pmid: 9757107
references.citation: Methods Enzymol. 1997;276:307-26
references.pmid: 27754618
references.citation: Antimicrob Agents Chemother. 2002 Jul;46(7):2124-31
references.pmid: 12069964
references.citation: FEMS Microbiol Lett. 2002 Jan 10;206(2):185-9
references.pmid: 11814661
references.citation: Nature. 2002 Oct 10;419(6907):587-93
references.pmid: 12374972
references.citation: J Mol Biol. 2014 Jan 23;426(2):403-11
references.pmid: 24099674
references.citation: J Biol Chem. 2011 Feb 18;286(7):5484-93
references.pmid: 21115481
references.citation: Nature. 2006 Sep 14;443(7108):173-9
references.pmid: 16915237
references.citation: PLoS Biol. 2007 Jan;5(1):e7
references.pmid: 17194213
references.citation: Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
references.pmid: 12393927
references.citation: J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
references.pmid: 19461840
references.citation: J Mol Biol. 2009 May 29;389(1):134-45
references.pmid: 19361527
references.citation: J Biol Chem. 2004 Jun 18;279(25):25939-42
references.pmid: 15117957