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Contributions of Counter-Charge in a Potassium Channel Voltage-Sensor Domain

Voltage-sensor domains couple membrane potential to conformational changes in voltage-gated ion channels and phosphatases. Highly co-evolved acidic and aromatic side-chains assist the transfer of cationic side-chains across the transmembrane electric field during voltage-sensing. We investigated the...

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Detalles Bibliográficos
Autores principales: Pless, Stephan A., Galpin, Jason D., Niciforovic, Ana P., Ahern, Christopher A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933587/
https://www.ncbi.nlm.nih.gov/pubmed/21785425
http://dx.doi.org/10.1038/nchembio.622
Descripción
Sumario:Voltage-sensor domains couple membrane potential to conformational changes in voltage-gated ion channels and phosphatases. Highly co-evolved acidic and aromatic side-chains assist the transfer of cationic side-chains across the transmembrane electric field during voltage-sensing. We investigated the functional contribution of negative electrostatic potentials from these residues to channel gating and voltage-sensing with unnatural amino acid mutagenesis, electrophysiology, voltage-clamp fluorometry and ab initio calculations. The data show that neutralization of two conserved acidic side-chains in transmembrane segments S2 and S3, Glu293 and Asp316 in Shaker potassium channels, have little functional effect on conductance-voltage relationships, although Glu293 appears to catalyze S4 movement. Our results suggest that neither Glu293 nor Asp316 engages in electrostatic state-dependent charge-charge interactions with S4, likely because they occupy, and possibly help create, a water-filled vestibule.