TY - JOUR
T1 - A gating hinge in Na+ channels
T2 - A molecular switch for electrical signaling
AU - Zhao, Yong
AU - Yarov-Yarovoy, Vladimir
AU - Scheuer, Todd
AU - Catterall, William A.
PY - 2004/3/25
Y1 - 2004/3/25
N2 - Voltage-gated sodium channels are members of a large family with similar pore structures. The mechanism of opening and closing is unknown, but structural studies suggest gating via bending of the inner pore helix at a glycine hinge. Here we provide functional evidence for this gating model for the bacterial sodium channel NaChBac. Mutation of glycine 219 to proline, which would strongly favor bending of the α helix, greatly enhances activation by shifting its voltage dependence -51 mV and slowing deactivation by 2000-fold. The mutation also slows voltage-dependent inactivation by 1200-fold. The effects are specific because substitutions of proline at neighboring positions and substitutions of other amino acids at position 219 have much smaller functional effects. Our results fit a model in which concerted bending at glycine 219 in the S6 segments of NaChBac serves as a gating hinge. This gating motion may be conserved in most members of this large ion channel protein family.
AB - Voltage-gated sodium channels are members of a large family with similar pore structures. The mechanism of opening and closing is unknown, but structural studies suggest gating via bending of the inner pore helix at a glycine hinge. Here we provide functional evidence for this gating model for the bacterial sodium channel NaChBac. Mutation of glycine 219 to proline, which would strongly favor bending of the α helix, greatly enhances activation by shifting its voltage dependence -51 mV and slowing deactivation by 2000-fold. The mutation also slows voltage-dependent inactivation by 1200-fold. The effects are specific because substitutions of proline at neighboring positions and substitutions of other amino acids at position 219 have much smaller functional effects. Our results fit a model in which concerted bending at glycine 219 in the S6 segments of NaChBac serves as a gating hinge. This gating motion may be conserved in most members of this large ion channel protein family.
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U2 - 10.1016/S0896-6273(04)00116-3
DO - 10.1016/S0896-6273(04)00116-3
M3 - Article
C2 - 15046719
AN - SCOPUS:1842422868
VL - 41
SP - 859
EP - 865
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 6
ER -