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.
Tao
Xiao
X
Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
Lee
Alice
A
Limapichat
Walrati
W
Dougherty
Dennis A
DA
MacKinnon
Roderick
R
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D025802:Electric Capacitance; D015640:Ion Channel Gating; D051663:Kv1.2 Potassium Channel / Q000737:chemistry* / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010649:Phenylalanine / Q000737:chemistry; D011487:Protein Conformation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D051669:Shab Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry; D014982:Xenopus laevis
C496991:Kcnb1 protein, rat; D051663:Kv1.2 Potassium Channel; D011993:Recombinant Fusion Proteins; D051669:Shab Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D010649:Phenylalanine; D014364:Tryptophan; D001120:Arginine; D008239:Lysine