Trapping Charge Mechanism in Hv1 Channels ( Ci Hv1)

The majority of voltage-gated ion channels contain a defined voltage-sensing domain and a pore domain composed of highly conserved amino acid residues that confer electrical excitability via electromechanical coupling. In this sense, the voltage-gated proton channel (Hv1) is a unique protein in that...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-12, Vol.25 (1), p.426
Main Authors: Fernández, Miguel, Alvear-Arias, Juan J, Carmona, Emerson M, Carrillo, Christian, Pena-Pichicoi, Antonio, Hernandez-Ochoa, Erick O, Neely, Alan, Alvarez, Osvaldo, Latorre, Ramon, Garate, Jose A, Gonzalez, Carlos
Format: Article
Language:English
Subjects:
Amino Acids
Animals
Antifibrinolytic Agents
Arginine
charge trapping
Charged particles
Ciona
Ciona intestinalis
Energy
gating currents
Mutation
Physiology
Potassium
proton channel
Protons
Sensors
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Summary:The majority of voltage-gated ion channels contain a defined voltage-sensing domain and a pore domain composed of highly conserved amino acid residues that confer electrical excitability via electromechanical coupling. In this sense, the voltage-gated proton channel (Hv1) is a unique protein in that voltage-sensing, proton permeation and pH-dependent modulation involve the same structural region. In fact, these processes synergistically work in concert, and it is difficult to separate them. To investigate the process of Hv1 voltage sensor trapping, we follow voltage-sensor movements directly by leveraging mutations that enable the measurement of Hv1 channel gating currents. We uncover that the process of voltage sensor displacement is due to two driving forces. The first reveals that mutations in the selectivity filter (D160) located in the S1 transmembrane interact with the voltage sensor. More hydrophobic amino acids increase the energy barrier for voltage sensor activation. On the other hand, the effect of positive charges near position 264 promotes the formation of salt bridges between the arginines of the voltage sensor domain, achieving a stable conformation over time. Our results suggest that the activation of the Hv1 voltage sensor is governed by electrostatic-hydrophobic interactions, and S4 arginines, N264 and selectivity filter (D160) are essential in the -Hv1 to understand the trapping of the voltage sensor.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25010426