Proteopedia

2fec

Structure of the E203Q mutant of the Cl-/H+ exchanger CLC-ec1 from E.ColiStructure of the E203Q mutant of the Cl-/H+ exchanger CLC-ec1 from E.Coli

Structural highlights

2fec is a 6 chain structure with sequence from Escherichia coli and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.967Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

CLC-ec1 is a prokaryotic CLC-type Cl(-)/H+ exchange transporter. Little is known about the mechanism of H+ coupling to Cl-. A critical glutamate residue, E148, was previously shown to be required for Cl(-)/H+ exchange by mediating proton transfer between the protein and the extracellular solution. To test whether an analogous H+ acceptor exists near the intracellular side of the protein, we performed a mutagenesis scan of inward-facing carboxyl-bearing residues and identified E203 as the unique residue whose neutralization abolishes H+ coupling to Cl- transport. Glutamate at this position is strictly conserved in all known CLCs of the transporter subclass, while valine is always found here in CLC channels. The x-ray crystal structure of the E203Q mutant is similar to that of the wild-type protein. Cl- transport rate in E203Q is inhibited at neutral pH, and the double mutant, E148A/E203Q, shows maximal Cl- transport, independent of pH, as does the single mutant E148A. The results argue that substrate exchange by CLC-ec1 involves two separate but partially overlapping permeation pathways, one for Cl- and one for H+. These pathways are congruent from the protein's extracellular surface to E148, and they diverge beyond this point toward the intracellular side. This picture demands a transport mechanism fundamentally different from familiar alternating-access schemes.

Separate ion pathways in a Cl-/H+ exchanger.,Accardi A, Walden M, Nguitragool W, Jayaram H, Williams C, Miller C J Gen Physiol. 2005 Dec;126(6):563-70. PMID:16316975[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ Accardi A, Walden M, Nguitragool W, Jayaram H, Williams C, Miller C. Separate ion pathways in a Cl-/H+ exchanger. J Gen Physiol. 2005 Dec;126(6):563-70. PMID:16316975 doi:10.1085/jgp.200509417

2fec, resolution 3.97Å

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