Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation
In response to hydrostatic pressure, the cation channel transient receptor potential vanilloid 1 (TRPV1) is essential in signaling pathways linked to glaucoma. When activated, TRPV1 undergoes a gating transition from a closed to an open state that allows the influx of Ca<sup>2+</sup> ion...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7366 |
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| author | Muhammad Harith Bin Zamri Yoshihiro Ujihara Masanori Nakamura Mohammad R. K. Mofrad Shukei Sugita |
| author_facet | Muhammad Harith Bin Zamri Yoshihiro Ujihara Masanori Nakamura Mohammad R. K. Mofrad Shukei Sugita |
| author_sort | Muhammad Harith Bin Zamri |
| collection | DOAJ |
| description | In response to hydrostatic pressure, the cation channel transient receptor potential vanilloid 1 (TRPV1) is essential in signaling pathways linked to glaucoma. When activated, TRPV1 undergoes a gating transition from a closed to an open state that allows the influx of Ca<sup>2+</sup> ions. However, the gating mechanism of TRPV1 in response to hydrostatic pressure at the molecular level is still lacking. To understand the effect of hydrostatic pressure on the activation of TRPV1, we conducted molecular-dynamics (MD) simulations on TRPV1 under different hydrostatic pressure configurations, with and without a cell membrane. The TRPV1 membrane-embedded model is more stable than the TPRV1-only model, indicating the importance of including the cell membrane in MD simulation. Under elevated pressure at 27.6 mmHg, we observed a more dynamic and outward motion of the TRPV1 domains in the lower-gate area than in the simulation under normal pressure at 12.6 mmHg. While a complete closed-to-open-gate transition was not evident in the limited course of our MD simulations, an increase in the channel radius at the lower gate was observed at 27.6 mmHg versus that at 12.6 mmHg. These findings provide novel information regarding the effect of hydrostatic pressure on TRPV1 channels. |
| first_indexed | 2024-03-09T21:48:11Z |
| format | Article |
| id | doaj.art-9a718c251a834e9eb334eeb9738a65cb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:48:11Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9a718c251a834e9eb334eeb9738a65cb2023-11-23T20:12:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012313736610.3390/ijms23137366Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics SimulationMuhammad Harith Bin Zamri0Yoshihiro Ujihara1Masanori Nakamura2Mohammad R. K. Mofrad3Shukei Sugita4Department of Electrical and Mechanical Engineering, Nagoya Institute of Technology, School of Engineering, Nagoya 466-8555, JapanDepartment of Electrical and Mechanical Engineering, Nagoya Institute of Technology, School of Engineering, Nagoya 466-8555, JapanDepartment of Electrical and Mechanical Engineering, Nagoya Institute of Technology, School of Engineering, Nagoya 466-8555, JapanDepartments of Bioengineering and Mechanical Engineering, University of California, Berkeley, CA 94720, USADepartment of Electrical and Mechanical Engineering, Nagoya Institute of Technology, School of Engineering, Nagoya 466-8555, JapanIn response to hydrostatic pressure, the cation channel transient receptor potential vanilloid 1 (TRPV1) is essential in signaling pathways linked to glaucoma. When activated, TRPV1 undergoes a gating transition from a closed to an open state that allows the influx of Ca<sup>2+</sup> ions. However, the gating mechanism of TRPV1 in response to hydrostatic pressure at the molecular level is still lacking. To understand the effect of hydrostatic pressure on the activation of TRPV1, we conducted molecular-dynamics (MD) simulations on TRPV1 under different hydrostatic pressure configurations, with and without a cell membrane. The TRPV1 membrane-embedded model is more stable than the TPRV1-only model, indicating the importance of including the cell membrane in MD simulation. Under elevated pressure at 27.6 mmHg, we observed a more dynamic and outward motion of the TRPV1 domains in the lower-gate area than in the simulation under normal pressure at 12.6 mmHg. While a complete closed-to-open-gate transition was not evident in the limited course of our MD simulations, an increase in the channel radius at the lower gate was observed at 27.6 mmHg versus that at 12.6 mmHg. These findings provide novel information regarding the effect of hydrostatic pressure on TRPV1 channels.https://www.mdpi.com/1422-0067/23/13/7366glaucomahydrostatic pressuremechanotransductionmolecular mechanics |
| spellingShingle | Muhammad Harith Bin Zamri Yoshihiro Ujihara Masanori Nakamura Mohammad R. K. Mofrad Shukei Sugita Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation International Journal of Molecular Sciences glaucoma hydrostatic pressure mechanotransduction molecular mechanics |
| title | Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation |
| title_full | Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation |
| title_fullStr | Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation |
| title_full_unstemmed | Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation |
| title_short | Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation |
| title_sort | decoding the effect of hydrostatic pressure on trpv1 lower gate conformation by molecular dynamics simulation |
| topic | glaucoma hydrostatic pressure mechanotransduction molecular mechanics |
| url | https://www.mdpi.com/1422-0067/23/13/7366 |
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