Structural highlights
Function
CLCA_ECOLI Proton-coupled chloride transporter. Functions as antiport system and exchanges two chloride ions for 1 proton. Probably acts as an electrical shunt for an outwardly-directed proton pump that is linked to amino acid decarboxylation, as part of the extreme acid resistance (XAR) response.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Cl-/H+ antiporters of the CLC superfamily transport anions across biological membranes in varied physiological contexts. These proteins are weakly selective among anions commonly studied, including Cl-, Br-, I-, NO3- and SCN-, but they seem to be very selective against F-. The recent discovery of a new CLC clade of F-/H+ antiporters, which are highly selective for F- over Cl-, led us to investigate the mechanism of Cl--over-F- selectivity by a CLC Cl-/H+ antiporter, CLC-ec1. By subjecting purified CLC-ec1 to anion transport measurements, electrophysiological recording, equilibrium ligand-binding studies and X-ray crystallography, we show that F- binds in the Cl- transport pathway with affinity similar to Cl- but stalls the transport cycle. Examination of various mutant antiporters implies a 'lock-down' mechanism of F- inhibition, in which F-, by virtue of its unique hydrogen-bonding chemistry, greatly retards a proton-linked conformational change essential for the transport cycle of CLC-ec1.
Fluoride-dependent interruption of the transport cycle of a CLC Cl/H antiporter.,Lim HH, Stockbridge RB, Miller C Nat Chem Biol. 2013 Sep 15. doi: 10.1038/nchembio.1336. PMID:24036509[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Iyer R, Iverson TM, Accardi A, Miller C. A biological role for prokaryotic ClC chloride channels. Nature. 2002 Oct 17;419(6908):715-8. PMID:12384697 doi:10.1038/nature01000
- ↑ Accardi A, Miller C. Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels. Nature. 2004 Feb 26;427(6977):803-7. PMID:14985752 doi:10.1038/nature02314
- ↑ Lobet S, Dutzler R. Ion-binding properties of the ClC chloride selectivity filter. EMBO J. 2006 Jan 11;25(1):24-33. Epub 2005 Dec 8. PMID:16341087
- ↑ Nguitragool W, Miller C. Uncoupling of a CLC Cl-/H+ exchange transporter by polyatomic anions. J Mol Biol. 2006 Sep 29;362(4):682-90. Epub 2006 Aug 14. PMID:16905147 doi:10.1016/j.jmb.2006.07.006
- ↑ Jayaram H, Accardi A, Wu F, Williams C, Miller C. Ion permeation through a Cl--selective channel designed from a CLC Cl-/H+ exchanger. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11194-9. Epub 2008 Aug 4. PMID:18678918
- ↑ Lim HH, Stockbridge RB, Miller C. Fluoride-dependent interruption of the transport cycle of a CLC Cl/H antiporter. Nat Chem Biol. 2013 Sep 15. doi: 10.1038/nchembio.1336. PMID:24036509 doi:http://dx.doi.org/10.1038/nchembio.1336
