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Title: Thermal actuation in $$\mathrm{TRPV1}$$: Role of embedded lipids and intracellular domains

Abstract

The transient response potential cation channel TRPV1 responds to high temperature, but many of the mechanisms driving its thermal actuation remain unclear. Its recently resolved structure has enabled a number of molecular dynamics (MD) studies focused on illuminating these mechanisms. Here we add to these efforts by performing the first all-atom MD simulations of its most recently resolved structure at different temperatures. While the complete, thermally induced transition of TRPV1 from its closed to open configuration remains elusive, our analysis of the hydrogen bonding networks, thermodynamics, hydration, and principal components of motion provide a wealth of information on the mechanisms which initiate or influence the thermal opening in TRPV1. In particular, we (i) support the previously proposed mechanism driving thermal actuation in the extracellular pore of TRPV1, (ii) present new hypotheses regarding the thermal actuation in the C-terminal and adjacent linker domains, and (iii) support and build upon the existing hypothesis regarding the role of the vanilloid binding pocket and lipids embedded therein.

Authors:
ORCiD logo [1]; ORCiD logo [1]
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  1. University of Michigan, Ann Arbor, MI (United States)
Publication Date:
Research Org.:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Oak Ridge Leadership Computing Facility (OLCF); Lawrence Berkeley National Laboratory, Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR); National Science Foundation (NSF)
OSTI Identifier:
1463865
Alternate Identifier(s):
OSTI ID: 1548710
Grant/Contract Number:  
AC05-00OR22725; AC02-05CH11231; CBET1332807
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Theoretical Biology
Additional Journal Information:
Journal Volume: 444; Journal Issue: C; Journal ID: ISSN 0022-5193
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; membrane protein; thermosensation; Ion channel; transient receptor potential

Citation Formats

Melnick, Corey, and Kaviany, Massoud. Thermal actuation in $\mathrm{TRPV1}$: Role of embedded lipids and intracellular domains. United States: N. p., 2018. Web. doi:10.1016/j.jtbi.2018.02.004.
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Melnick, Corey, & Kaviany, Massoud. Thermal actuation in $\mathrm{TRPV1}$: Role of embedded lipids and intracellular domains. United States. https://doi.org/10.1016/j.jtbi.2018.02.004
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Melnick, Corey, and Kaviany, Massoud. Tue . "Thermal actuation in $\mathrm{TRPV1}$: Role of embedded lipids and intracellular domains". United States. https://doi.org/10.1016/j.jtbi.2018.02.004. https://www.osti.gov/servlets/purl/1463865.
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@article{osti_1463865,
title = {Thermal actuation in $\mathrm{TRPV1}$: Role of embedded lipids and intracellular domains},
author = {Melnick, Corey and Kaviany, Massoud},
abstractNote = {The transient response potential cation channel TRPV1 responds to high temperature, but many of the mechanisms driving its thermal actuation remain unclear. Its recently resolved structure has enabled a number of molecular dynamics (MD) studies focused on illuminating these mechanisms. Here we add to these efforts by performing the first all-atom MD simulations of its most recently resolved structure at different temperatures. While the complete, thermally induced transition of TRPV1 from its closed to open configuration remains elusive, our analysis of the hydrogen bonding networks, thermodynamics, hydration, and principal components of motion provide a wealth of information on the mechanisms which initiate or influence the thermal opening in TRPV1. In particular, we (i) support the previously proposed mechanism driving thermal actuation in the extracellular pore of TRPV1, (ii) present new hypotheses regarding the thermal actuation in the C-terminal and adjacent linker domains, and (iii) support and build upon the existing hypothesis regarding the role of the vanilloid binding pocket and lipids embedded therein.},
doi = {10.1016/j.jtbi.2018.02.004},
journal = {Journal of Theoretical Biology},
number = C,
volume = 444,
place = {United States},
year = {Tue Feb 06 00:00:00 EST 2018},
month = {Tue Feb 06 00:00:00 EST 2018}
}
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https://doi.org/10.1016/j.jtbi.2018.02.004
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    Works referencing / citing this record:

    Emerging Diversity in Lipid–Protein Interactions
    journal, January 2019

    Proximal C-Terminus Serves as a Signaling Hub for TRPA1 Channel Regulation via Its Interacting Molecules and Supramolecular Complexes
    journal, March 2020

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