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Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel.

Nadezhdin KD, Neuberger A, Trofimov YA, Krylov NA, Sinica V, Kupko N, Vlachova V, Zakharian E, Efremov RG, Sobolevsky AI
Nat Struct Mol Biol 28 564-572 (2021)
Related entries: 7mik, 7mil, 7mim, 7min, 7mio

Cited: 60 times
EuropePMC logo PMID: 34239124

Abstract

Numerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been studied extensively, structural determination of their heat- and cold-activated states has remained a challenge. Here, we present cryo-EM structures of the nanodisc-reconstituted wild-type mouse TRPV3 in three distinct conformations: closed, heat-activated sensitized and open states. The heat-induced transformations of TRPV3 are accompanied by changes in the secondary structure of the S2-S3 linker and the N and C termini and represent a conformational wave that links these parts of the protein to a lipid occupying the vanilloid binding site. State-dependent differences in the behavior of bound lipids suggest their active role in thermo-TRP temperature-dependent gating. Our structural data, supported by physiological recordings and molecular dynamics simulations, provide an insight for understanding the molecular mechanism of temperature sensing.

Reviews - 7mij mentioned but not cited (1)

  1. Ligand-Binding Sites in Vanilloid-Subtype TRP Channels. Yelshanskaya MV, Sobolevsky AI. Front Pharmacol 13 900623 (2022)

Articles - 7mij mentioned but not cited (4)



Reviews citing this publication (14)

  1. Regulation of membrane protein structure and function by their lipid nano-environment. Levental I, Lyman E. Nat Rev Mol Cell Biol 24 107-122 (2023)
  2. TRP channels: a journey towards a molecular understanding of pain. Rosenbaum T, Morales-Lázaro SL, Islas LD. Nat Rev Neurosci 23 596-610 (2022)
  3. Sensory TRP Channels in Three Dimensions. Diver MM, Lin King JV, Julius D, Cheng Y. Annu Rev Biochem 91 629-649 (2022)
  4. Druggable Lipid Binding Sites in Pentameric Ligand-Gated Ion Channels and Transient Receptor Potential Channels. Cheng WWL, Arcario MJ, Petroff JT. Front Physiol 12 798102 (2021)
  5. Insights into the Role of Membrane Lipids in the Structure, Function and Regulation of Integral Membrane Proteins. Renard K, Byrne B. Int J Mol Sci 22 9026 (2021)
  6. Membranes under the Magnetic Lens: A Dive into the Diverse World of Membrane Protein Structures Using Cryo-EM. Piper SJ, Johnson RM, Wootten D, Sexton PM. Chem Rev 122 13989-14017 (2022)
  7. Progress in the Structural Basis of thermoTRP Channel Polymodal Gating. Fernández-Ballester G, Fernández-Carvajal A, Ferrer-Montiel A. Int J Mol Sci 24 743 (2023)
  8. TRPV3 Ion Channel: From Gene to Pharmacology. Kalinovskii AP, Utkina LL, Korolkova YV, Andreev YA. Int J Mol Sci 24 8601 (2023)
  9. Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms. Huang J, Korsunsky A, Yazdani M, Chen J. Front Mol Neurosci 16 1334370 (2023)
  10. Designer Nanodiscs to Probe and Reprogram Membrane Biology in Synapses. Dallo S, Shin J, Zhang S, Ren Q, Bao H. J Mol Biol 435 167757 (2023)
  11. Dilation of ion selectivity filters in cation channels. Huffer K, Tan XF, Fernández-Mariño AI, Dhingra S, Swartz KJ. Trends Biochem Sci 49 417-430 (2024)
  12. Graph Neural Networks as a Potential Tool in Improving Virtual Screening Programs. Alves LA, Ferreira NCDS, Maricato V, Alberto AVP, Dias EA, Jose Aguiar Coelho N. Front Chem 9 787194 (2021)
  13. Human Transient Receptor Potential Ankyrin 1 Channel: Structure, Function, and Physiology. Vlachova V, Barvik I, Zimova L. Subcell Biochem 104 207-244 (2024)
  14. Vertebrate behavioral thermoregulation: knowledge and future directions. Cutler B, Haesemeyer M. Neurophotonics 11 033409 (2024)

Articles citing this publication (41)



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