4KKL: Structure Of The E148a Mutant Of Clc-ec1 Delta Nc Construct In 100mm Fluoride

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.
PDB ID: 4KKLDownload
MMDB ID: 112846
PDB Deposition Date: 2013/5/6
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 2.85  Å
Source Organism:
Escherichia coli K-12
Similar Structures:
Biological Unit for 4KKL: dimeric; determined by author and by software (PISA)
Molecular Components in 4KKL
Label Count Molecule
Proteins (2 molecules)
H(+)/cl(-) Exchange Transporter Clca(Gene symbol: clcA)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

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