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Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.

Publication ,  Journal Article
Kwon, DH; Zhang, F; Fedor, JG; Suo, Y; Lee, S-Y
Published in: Nat Commun
May 24, 2022

Single particle cryo-EM often yields multiple protein conformations within a single dataset, but experimentally deducing the temporal relationship of these conformers within a conformational trajectory is not trivial. Here, we use thermal titration methods and cryo-EM in an attempt to obtain temporal resolution of the conformational trajectory of the vanilloid receptor TRPV1 with resiniferatoxin (RTx) bound. Based on our cryo-EM ensemble analysis, RTx binding to TRPV1 appears to induce intracellular gate opening first, followed by selectivity filter dilation, then pore loop rearrangement to reach the final open state. This apparent conformational wave likely arises from the concerted, stepwise, additive structural changes of TRPV1 over many subdomains. Greater understanding of the RTx-mediated long-range allostery of TRPV1 could help further the therapeutic potential of RTx, which is a promising drug candidate for pain relief associated with advanced cancer or knee arthritis.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 24, 2022

Volume

13

Issue

1

Start / End Page

2874

Location

England

Related Subject Headings

  • TRPV Cation Channels
  • Protein Conformation
  • Diterpenes
  • Cryoelectron Microscopy
  • Biochemical Phenomena
 

Citation

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Kwon, D. H., Zhang, F., Fedor, J. G., Suo, Y., & Lee, S.-Y. (2022). Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis. Nat Commun, 13(1), 2874. https://doi.org/10.1038/s41467-022-30602-2
Kwon, Do Hoon, Feng Zhang, Justin G. Fedor, Yang Suo, and Seok-Yong Lee. “Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.Nat Commun 13, no. 1 (May 24, 2022): 2874. https://doi.org/10.1038/s41467-022-30602-2.
Kwon DH, Zhang F, Fedor JG, Suo Y, Lee S-Y. Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis. Nat Commun. 2022 May 24;13(1):2874.
Kwon, Do Hoon, et al. “Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.Nat Commun, vol. 13, no. 1, May 2022, p. 2874. Pubmed, doi:10.1038/s41467-022-30602-2.
Kwon DH, Zhang F, Fedor JG, Suo Y, Lee S-Y. Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis. Nat Commun. 2022 May 24;13(1):2874.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 24, 2022

Volume

13

Issue

1

Start / End Page

2874

Location

England

Related Subject Headings

  • TRPV Cation Channels
  • Protein Conformation
  • Diterpenes
  • Cryoelectron Microscopy
  • Biochemical Phenomena