4KKB

Structure of the E148A mutant of CLC-ec1 deltaNC construct in 20mM fluoride and 20mM Bromide

4KKB の概要

• エントリーDOI: 10.2210/pdb4kkb/pdb
• 関連するPDBエントリー: 4KJP 4KJQ 4KJW 4KK5 4KK6 4KK8 4KK9 4KKA 4KKC
• 分子名称: H(+)/Cl(-) exchange transporter ClcA, Fab, heavy chain, Fab, light chain (3 entities in total)
• 機能のキーワード: membrane transporter, transport protein
• 由来する生物種: Escherichia coli; 詳細
• 細胞内の位置: Cell inner membrane; Multi-pass membrane protein (Probable): P37019
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 188943.68

構造登録者

Lim, H.-H.,Miller, C. (登録日: 2013-05-05, 公開日: 2013-08-21, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.021 Å)