Electrostatic interactions of S4 voltage sensor in Shaker K+ channel
| Autor: | Yu Huang, Diane M. Papazian, Allan F. Mock, Daniel H Wainstock, Sang-Ah Seoh, Xuesi M. Shao |
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| Rok vydání: | 1995 |
| Předmět: |
Potassium Channels
Protein Conformation Neuroscience(all) Xenopus 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Voltage sensor Electrochemistry Animals Shaker 030304 developmental biology K channels Genetics 0303 health sciences Double mutant Chemistry General Neuroscience Gene Transfer Techniques Electrostatics Transmembrane protein Folding (chemistry) Electrophysiology Mutagenesis Biophysics Oocytes Genetic selection 030217 neurology & neurosurgery |
| Zdroj: | Neuron. 14(6) |
| ISSN: | 0896-6273 |
| Popis: | The S4 segment comprises part of the voltage sensor in Shaker K + channels. We have used a strategy similar to intragenic suppression, but without a genetic selection, to identify electrostatic interactions of the S4 segment that may be important in the mechanism of voltage-dependent activation. The S4 neutralization mutations K374Q and R3770 block maturation of the protein, suggesting that they prevent proper folding. K374Q is specifically and efficiently rescued by the second site mutations E2930 and D316N, located in putative transmembrane segments S2 and S3, respectively. These results suggest that K374, E293, and D316 form a network of strong, local, electrostatic interactions that stabilize the structure of the channel. Some other double mutant combinations result in inefficient suppression, identifying weak, presumably longrange electrostatic interactions. A simple structural hypothesis is proposed to account forthe effects of the rescued double mutant combinations on the relative stabilities of open and closed channel conformations. |
| Databáze: | OpenAIRE |
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