 |
PDBsum entry 4kjp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Tranport protein, membrane protein
|
PDB id
|
|
|
|
4kjp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
443 a.a.
|
|
|
|
|
|
|
|
|
|
|
221 a.a.
|
|
|
|
|
|
|
|
|
|
|
211 a.a.
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Fluoride-Dependent interruption of the transport cycle of a clc cl-/H+ antiporter.
|
|
|
Authors
|
|
H.H.Lim,
R.B.Stockbridge,
C.Miller.
|
|
|
Ref.
|
|
Nat Chem Biol, 2013,
9,
721-725.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
