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Strong cooperativity between subunits in voltage-gated proton channels
Carlos Gonzalez1, Hans P Koch, Ben M Drum
1Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Nature Structural & Molecular Biology
|December 22, 2009
Summary
Voltage-activated proton (Hv) channels require both subunits to move for activation in dimeric forms. Preventing dimerization allows single subunit activation, revealing strong cooperativity in Hv channel function.
Area of Science:
- Ion channel biophysics
- Innate immunity mechanisms
- Cellular electrophysiology
Background:
- Voltage-activated proton (Hv) channels are crucial for innate immune responses.
- Hv channels function as dimers, each with a proton permeation pathway.
- The mechanism of voltage activation and inter-subunit cooperation remains unclear.
Purpose of the Study:
- To investigate the voltage-sensing mechanism of Ciona intestinalis Hv channels.
- To determine the role of subunit cooperation in Hv channel activation.
- To elucidate how voltage triggers proton flow through Hv channels.
Main Methods:
- Cysteine accessibility measurements to probe protein structure.
- Voltage-clamp fluorometry to monitor channel gating.
- Functional analysis of dimeric versus non-dimeric Hv channel constructs.
Main Results:
- The fourth transmembrane segment (S4) likely acts as the voltage sensor.
- In dimeric Hv channels, S4 movement in both subunits is necessary for activation.
- Disrupting dimerization allows single S4 movement to activate a proton pathway.
Conclusions:
- Strong cooperativity exists between subunits in dimeric Hv channels.
- Hv channel activation involves coordinated voltage sensing across subunits.
- Understanding Hv channel gating is key to innate immunity research.
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