Trapping Charge Mechanism in Hv1 Channels (<i>Ci</i>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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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/426 |
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| author | Miguel Fernández Juan J. Alvear-Arias Emerson M. Carmona Christian Carrillo Antonio Pena-Pichicoi Erick O. Hernandez-Ochoa Alan Neely Osvaldo Alvarez Ramon Latorre Jose A. Garate Carlos Gonzalez |
| author_facet | Miguel Fernández Juan J. Alvear-Arias Emerson M. Carmona Christian Carrillo Antonio Pena-Pichicoi Erick O. Hernandez-Ochoa Alan Neely Osvaldo Alvarez Ramon Latorre Jose A. Garate Carlos Gonzalez |
| author_sort | Miguel Fernández |
| collection | DOAJ |
| description | 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 <i>Ciona</i>-Hv1 to understand the trapping of the voltage sensor. |
| first_indexed | 2024-03-08T15:05:44Z |
| format | Article |
| id | doaj.art-d70dfb18b1174728b2b0ac802e261aaf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:44Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d70dfb18b1174728b2b0ac802e261aaf2024-01-10T14:59:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125142610.3390/ijms25010426Trapping Charge Mechanism in Hv1 Channels (<i>Ci</i>Hv1)Miguel Fernández0Juan J. Alvear-Arias1Emerson M. Carmona2Christian Carrillo3Antonio Pena-Pichicoi4Erick O. Hernandez-Ochoa5Alan Neely6Osvaldo Alvarez7Ramon Latorre8Jose A. Garate9Carlos Gonzalez10Centro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso 2351319, ChileCentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso 2351319, ChileCell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USACentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso 2351319, ChileCentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso 2351319, ChileDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USACentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso 2351319, ChileCentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso 2351319, ChileCentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso 2351319, ChileFacultad de Ingeniería, Arquitectura y Diseño, Universidad San Sebastian, Santiago 7780272, ChileMillennium Nucleus in NanoBioPhysics, Universidad de Valparaíso, Valparaíso 2351319, ChileThe 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 <i>Ciona</i>-Hv1 to understand the trapping of the voltage sensor.https://www.mdpi.com/1422-0067/25/1/426<i>Ciona intestinalis</i>proton channelgating currentscharge trapping |
| spellingShingle | Miguel Fernández Juan J. Alvear-Arias Emerson M. Carmona Christian Carrillo Antonio Pena-Pichicoi Erick O. Hernandez-Ochoa Alan Neely Osvaldo Alvarez Ramon Latorre Jose A. Garate Carlos Gonzalez Trapping Charge Mechanism in Hv1 Channels (<i>Ci</i>Hv1) International Journal of Molecular Sciences <i>Ciona intestinalis</i> proton channel gating currents charge trapping |
| title | Trapping Charge Mechanism in Hv1 Channels (<i>Ci</i>Hv1) |
| title_full | Trapping Charge Mechanism in Hv1 Channels (<i>Ci</i>Hv1) |
| title_fullStr | Trapping Charge Mechanism in Hv1 Channels (<i>Ci</i>Hv1) |
| title_full_unstemmed | Trapping Charge Mechanism in Hv1 Channels (<i>Ci</i>Hv1) |
| title_short | Trapping Charge Mechanism in Hv1 Channels (<i>Ci</i>Hv1) |
| title_sort | trapping charge mechanism in hv1 channels i ci i hv1 |
| topic | <i>Ciona intestinalis</i> proton channel gating currents charge trapping |
| url | https://www.mdpi.com/1422-0067/25/1/426 |
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