XB-ART-41459Science. April 2, 2010; 328 (5974): 67-73.
A gating charge transfer center in voltage sensors.
Voltage sensors regulate the conformations of voltage-dependent ion channels and enzymes. Their nearly switchlike response as a function of membrane voltage comes from the movement of positively charged amino acids, arginine or lysine, across the membrane field. We used mutations with natural and unnatural amino acids, electrophysiological recordings, and x-ray crystallography to identify a charge transfer center in voltage sensors that facilitates this movement. This center consists of a rigid cyclic "cap" and two negatively charged amino acids to interact with a positive charge. Specific mutations induce a preference for lysine relative to arginine. By placing lysine at specific locations, the voltage sensor can be stabilized in different conformations, which enables a dissection of voltage sensor movements and their relation to ion channel opening.
PubMed ID: 20360102
PMC ID: PMC2869078
Article link: Science.
Grant support: GM43949 NIGMS NIH HHS , NS 34407 NINDS NIH HHS , Howard Hughes Medical Institute , R01 GM043949-20 NIGMS NIH HHS , R37 NS034407-15 NINDS NIH HHS , R37 NS034407-15S1 NINDS NIH HHS , R01 GM043949 NIGMS NIH HHS , P30 EB009998 NIBIB NIH HHS , R37 NS034407 NINDS NIH HHS , R01 NS034407 NINDS NIH HHS , HHMI_MACKINNON_R Howard Hughes Medical Institute