Large movement in the C terminus of CLC-0 chloride channel during slow gating.
Chloride channels and transporters of the CLC gene family are expressed in virtually all cell types and are crucial in the regulation of membrane potential, chloride homeostasis and intravesicular pH. There are two gating processes that open CLC channels-fast and slow. The fast gating process in CLC channels has recently been linked to a small movement of a glutamate side chain. However, the molecular mechanism underlying the slow gating process is still elusive. Using spectroscopic microscopy, we observed a large backbone movement in the C terminus of the CLC-0 chloride channel that was functionally linked to slow gating. We further showed that the C-terminal movement had a time course similar to slow gating. In addition, a mutation known to lock the slow gate open prevented movement of the C terminus. When combined with recent structural information on the CLC C terminus, our findings provide a structural model for understanding the conformational changes linked to slow gating in CLC transport proteins.
Bykova
Ekaterina A
EA
Department of Physiology and Membrane Biology, University of California, Davis, California 95616, USA.
Zhang
Xiao-Dong
XD
Chen
Tsung-Yu
TY
Zheng
Jie
J
D002460:Cell Line; D018118:Chloride Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D015640:Ion Channel Gating; D008958:Models, Molecular; D018408:Patch-Clamp Techniques; D020836:Protein Structure, Quaternary
D018118:Chloride Channels