%0 Journal Article %1 Lee09PBTwo %A Lee, Seok-Yong %A Banerjee, Anirban %A MacKinnon, Roderick %D 2009 %J PLoS Biol. %K VoltageGating KChannels %N 3 %P e47 %R 10.1371/journal.pbio.1000047 %T Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent K$^+$ channels. %U http://dx.doi.org/10.1371/journal.pbio.1000047 %V 7 %X Voltage-dependent K(+) (Kv) channels gate open in response to the membrane voltage. To further our understanding of how cell membrane voltage regulates the opening of a Kv channel, we have studied the protein interfaces that attach the voltage-sensor domains to the pore. In the crystal structure, three physical interfaces exist. Only two of these consist of amino acids that are co-evolved across the interface between voltage sensor and pore according to statistical coupling analysis of 360 Kv channel sequences. A first co-evolved interface is formed by the S4-S5 linkers (one from each of four voltage sensors), which form a cuff surrounding the S6-lined pore opening at the intracellular surface. The crystal structure and published mutational studies support the hypothesis that the S4-S5 linkers convert voltage-sensor motions directly into gate opening and closing. A second co-evolved interface forms a small contact surface between S1 of the voltage sensor and the pore helix near the extracellular surface. We demonstrate through mutagenesis that this interface is necessary for the function and/or structure of two different Kv channels. This second interface is well positioned to act as a second anchor point between the voltage sensor and the pore, thus allowing efficient transmission of conformational changes to the pore's gate.

@article{Lee09PBTwo, abstract = {Voltage-dependent K(+) (Kv) channels gate open in response to the membrane voltage. To further our understanding of how cell membrane voltage regulates the opening of a Kv channel, we have studied the protein interfaces that attach the voltage-sensor domains to the pore. In the crystal structure, three physical interfaces exist. Only two of these consist of amino acids that are co-evolved across the interface between voltage sensor and pore according to statistical coupling analysis of 360 Kv channel sequences. A first co-evolved interface is formed by the S4-S5 linkers (one from each of four voltage sensors), which form a cuff surrounding the S6-lined pore opening at the intracellular surface. The crystal structure and published mutational studies support the hypothesis that the S4-S5 linkers convert voltage-sensor motions directly into gate opening and closing. A second co-evolved interface forms a small contact surface between S1 of the voltage sensor and the pore helix near the extracellular surface. We demonstrate through mutagenesis that this interface is necessary for the function and/or structure of two different Kv channels. This second interface is well positioned to act as a second anchor point between the voltage sensor and the pore, thus allowing efficient transmission of conformational changes to the pore's gate.}, added-at = {2009-10-05T08:00:36.000+0200}, author = {Lee, Seok-Yong and Banerjee, Anirban and MacKinnon, Roderick}, biburl = {https://www.bibsonomy.org/bibtex/218640d17dcf2001aeacacbd2f8fe7bb1/zwy}, doi = {10.1371/journal.pbio.1000047}, file = {Lee09PBTwo.pdf:channels/Lee09PBTwo.pdf:PDF}, institution = {Howard Hughes Medical Institute, Rockefeller University, New York, NY, USA.}, interhash = {000b6e68f1d09d4d936a31f0a04ae358}, intrahash = {18640d17dcf2001aeacacbd2f8fe7bb1}, journal = {PLoS Biol.}, keywords = {VoltageGating KChannels}, language = {eng}, medline-pst = {ppublish}, month = Mar, number = 3, pages = {e47}, pdf = {channels/Lee09PBTwo.pdf}, pii = {08-PLBI-RA-4209}, pmid = {19260762}, review = {VG Channel中的几个对功能重要的界面。指出电场力的传递路线}, timestamp = {2009-10-05T08:00:36.000+0200}, title = {Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent {K$^+$} channels.}, url = {http://dx.doi.org/10.1371/journal.pbio.1000047}, volume = 7, year = 2009 }