4KJP

Structure of the CLC-ec1 deltaNC construct in the absence of halide

Summary for 4KJP

• Entry DOI: 10.2210/pdb4kjp/pdb
• Related: 4KJP 4KJQ 4KJW 4KK5 4KK6 4KK8 4KK9 4KKA 4KKB
• Descriptor: H(+)/Cl(-) exchange transporter ClcA, heavy chain of Fab fragment, light chain of Fab fragment (3 entities in total)
• Functional Keywords: membrane transporting protein, tranport protein, membrane protein
• Biological source: Escherichia coli; More
• Cellular location: Cell inner membrane ; Multi- pass membrane protein : P37019
• Total number of polymer chains: 6
• Total formula weight: 189059.75

Authors

Lim, H.-H.,Miller, C. (deposition date: 2013-05-03, release date: 2013-08-21, Last modification date: 2024-11-20)

Primary citation

Lim, H.H.,Stockbridge, R.B.,Miller, C.
Fluoride-dependent interruption of the transport cycle of a CLC Cl(-)/H(+) antiporter.
Nat.Chem.Biol., 9:721-725, 2013

PubMed Abstract: 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.

PubMed: 24036509
DOI: 10.1038/nchembio.1336

Experimental method

X-RAY DIFFRACTION (3.2 Å)