TY - JOUR
T1 - The influence of lipids on voltage-gated ion channels
AU - Jiang, Qiu Xing
AU - Gonen, Tamir
N1 - Funding Information:
Because of limited space we were not able to cite the large body of published work by many of our colleagues on the topics discussed here. The authors want to thank Dr. Liang Shi for his help in preparing the figures. The cryoEM work in Dr. Jiang's lab on the Kv channels is funded by NIH ( R01GM088745 and R01GM093271 ). Dr. Gonen's group is supported by the Howard Hughes Medical Institute.
PY - 2012/8
Y1 - 2012/8
N2 - Voltage-gated ion channels are responsible for transmitting electrochemical signals in both excitable and non-excitable cells. Structural studies of voltage-gated potassium and sodium channels by X-ray crystallography have revealed atomic details on their voltage-sensor domains (VSDs) and pore domains, and were put in context of disparate mechanistic views on the voltage-driven conformational changes in these proteins. Functional investigation of voltage-gated channels in membranes, however, showcased a mechanism of lipid-dependent gating for voltage-gated channels, suggesting that the lipids play an indispensible and critical role in the proper gating of many of these channels. Structure determination of membrane-embedded voltage-gated ion channels appears to be the next frontier in fully addressing the mechanism by which the VSDs control channel opening. Currently electron crystallography is the only structural biology method in which a membrane protein of interest is crystallized within a complete lipid-bilayer mimicking the native environment of a biological membrane. At a sufficiently high resolution, an electron crystallographic structure could reveal lipids, the channel and their mutual interactions at the atomic level. Electron crystallography is therefore a promising avenue toward understanding how lipids modulate channel activation through close association with the VSDs.
AB - Voltage-gated ion channels are responsible for transmitting electrochemical signals in both excitable and non-excitable cells. Structural studies of voltage-gated potassium and sodium channels by X-ray crystallography have revealed atomic details on their voltage-sensor domains (VSDs) and pore domains, and were put in context of disparate mechanistic views on the voltage-driven conformational changes in these proteins. Functional investigation of voltage-gated channels in membranes, however, showcased a mechanism of lipid-dependent gating for voltage-gated channels, suggesting that the lipids play an indispensible and critical role in the proper gating of many of these channels. Structure determination of membrane-embedded voltage-gated ion channels appears to be the next frontier in fully addressing the mechanism by which the VSDs control channel opening. Currently electron crystallography is the only structural biology method in which a membrane protein of interest is crystallized within a complete lipid-bilayer mimicking the native environment of a biological membrane. At a sufficiently high resolution, an electron crystallographic structure could reveal lipids, the channel and their mutual interactions at the atomic level. Electron crystallography is therefore a promising avenue toward understanding how lipids modulate channel activation through close association with the VSDs.
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U2 - 10.1016/j.sbi.2012.03.009
DO - 10.1016/j.sbi.2012.03.009
M3 - Review article
C2 - 22483432
AN - SCOPUS:84865301019
SN - 0959-440X
VL - 22
SP - 529
EP - 536
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
IS - 4
ER -