title: The coupled proton transport in the ClC-ec1 Cl(-)/H(+) antiporter.
abstract: Using a reactive molecular dynamics simulation methodology, the free energy barrier for water-mediated proton transport between the two proton gating residues Glu(203) and Glu(148) in the ClC-ec1 antiporter, including the Grotthuss mechanism of proton hopping, was calculated. Three different chloride-binding states, with 1), both the central and internal Cl(-), 2), the central Cl(-) only, and 3), the internal Cl(-) only, were considered and the coupling to the H(+) transport studied. The results show that both the central and internal Cl(-) are essential for the proton transport from Glu(203) to Glu(148) to have a favorite free energy driving force. The rotation of the Glu(148) side chain was also found to be independent of the internal chloride binding state. These results emphasize the importance of the 2:1 stoichiometry of this well-studied Cl(-)/H(+) antiporter.
authors.affiliation: Department of Chemistry, James Franck Institute, Institute for Biophysical Dynamics, and Computation Institute, University of Chicago, Chicago, Illinois, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D017920:Antiporters / Q000737:chemistry / Q000378:metabolism*; D018118:Chloride Channels / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D017136:Ion Transport; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011522:Protons; D013816:Thermodynamics
chemical_list: D017920:Antiporters; C570787:CLC-ec1 protein, E coli; D018118:Chloride Channels; D029968:Escherichia coli Proteins; D050505:Mutant Proteins; D011522:Protons; D018698:Glutamic Acid
references.citation: Biophys J. 2009 Jul 8;97(1):121-31
references.pmid: 19580750
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Jan 27;364(1514):175-80
references.pmid: 18977737
references.citation: Biophys J. 2010 Mar 17;98(6):999-1008
references.pmid: 20303857
references.citation: J Mol Biol. 2004 Jun 11;339(4):981-1000
references.pmid: 15165864
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20659-65
references.pmid: 18093952
references.citation: Biophys J. 2004 Feb;86(2):836-45
references.pmid: 14747319
references.citation: Biophys J. 2010 Jul 21;99(2):464-71
references.pmid: 20643064
references.citation: Proteins. 2004 Nov 1;57(2):414-21
references.pmid: 15340928
references.citation: J Biol Chem. 2011 Jan 28;286(4):2976-86
references.pmid: 21059656
references.citation: J Gen Physiol. 2007 Apr;129(4):317-29
references.pmid: 17389248
references.citation: Nature. 2002 Jan 17;415(6869):287-94
references.pmid: 11796999
references.citation: Nature. 2004 Feb 26;427(6977):803-7
references.pmid: 14985752
references.citation: J Gen Physiol. 2005 Dec;126(6):563-70
references.pmid: 16316975
references.citation: Science. 2003 Apr 4;300(5616):108-12
references.pmid: 12649487
references.citation: Curr Opin Neurobiol. 2005 Jun;15(3):319-25
references.pmid: 15913981
references.citation: J Mol Biol. 2006 Aug 11;361(2):390-8
references.pmid: 16843488
references.citation: J Gen Physiol. 2009 Feb;133(2):131-8
references.pmid: 19139174
references.citation: Nat Struct Mol Biol. 2006 Dec;13(12):1115-9
references.pmid: 17115052
references.citation: Biophys J. 2004 Sep;87(3):1686-96
references.pmid: 15345547
references.citation: J Mol Biol. 2006 Sep 29;362(4):691-9
references.pmid: 16949616
references.citation: Science. 2010 Oct 29;330(6004):635-41
references.pmid: 20929736