Structural determinants of voltage-gating properties in calcium channels
- Medical University Innsbruck, Austria
- University of Innsbruck, Austria
Abstract
Voltage-gated calcium channels control key functions of excitable cells, like synaptic transmission in neurons and the contraction of heart and skeletal muscles. To accomplish such diverse functions, different calcium channels activate at different voltages and with distinct kinetics. To identify the molecular mechanisms governing specific voltage-sensing properties we combined structure modeling, mutagenesis, and electrophysiology to analyze the structures, free energy, and transition kinetics of the activated and resting states of two functionally distinct voltage-sensing domains (VSDs) of the eukaryotic calcium channel CaV1.1. Both VSDs displayed the typical features of the sliding helix model; however, they greatly differed in ion-pair formation of the outer gating charges. Specifically, stabilization of the activated state enhanced the voltage-dependence of activation, while stabilization of resting states slowed the kinetics. This mechanism provides a mechanistic model explaining how specific ion-pair formation in separate VSDs can realize the characteristic gating properties of voltage-gated cation channels.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. The pdb structures of the models of the activated and the resting states of both the WT VSDs and the mutants are available from the Dryad server https://doi.org/10.5061/dryad.hhmgqnkfd.
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Structural determinants of voltage-gating properties in calcium channelsDryad Digital Repository, 10.5061/dryad.hhmgqnkfd.
Article and author information
Author details
Monica L Fernández-Quintero
Bernhard E Flucher
Funding
Austrian Science Fund (P30402)
- Bernhard E Flucher
Austrian Science Fund (DOC30)
- Bernhard E Flucher
Austrian Science Fund (T855)
- Marta Campiglio
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Fernández-Quintero et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural determinants of voltage-gating properties in calcium channels
eLife 10:e64087.
https://doi.org/10.7554/eLife.64087
