Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 859-865 |
| Number of pages | 7 |
| Journal | Neuron |
| Volume | 41 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 25 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
Cite this
A gating hinge in Na+ channels : A molecular switch for electrical signaling. / Zhao, Yong; Yarov-Yarovoy, Vladimir; Scheuer, Todd; Catterall, William A.
In: Neuron, Vol. 41, No. 6, 25.03.2004, p. 859-865.Research output: Contribution to journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=1842422868&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842422868&partnerID=8YFLogxK
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 -