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Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel.

Publication ,  Journal Article
Yin, Y; Wu, M; Hsu, AL; Borschel, WF; Borgnia, MJ; Lander, GC; Lee, S-Y
Published in: Nat Commun
August 20, 2019

The transient receptor potential melastatin 2 (TRPM2) channel plays a key role in redox sensation in many cell types. Channel activation requires binding of both ADP-ribose (ADPR) and Ca2+. The recently published TRPM2 structures from Danio rerio in the ligand-free and the ADPR/Ca2+-bound conditions represent the channel in closed and open states, which uncovered substantial tertiary and quaternary conformational rearrangements. However, it is unclear how these rearrangements are achieved within the tetrameric channel during channel gating. Here we report the cryo-electron microscopy structures of Danio rerio TRPM2 in the absence of ligands, in complex with Ca2+ alone, and with both ADPR and Ca2+, resolved to ~4.3 Å, ~3.8 Å, and ~4.2 Å, respectively. In contrast to the published results, our studies capture ligand-bound TRPM2 structures in two-fold symmetric intermediate states, offering a glimpse of the structural transitions that bridge the closed and open conformations.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 20, 2019

Volume

10

Issue

1

Start / End Page

3740

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • TRPM Cation Channels
  • Spodoptera
  • Sf9 Cells
  • Protein Structure, Quaternary
  • Patch-Clamp Techniques
  • Ion Channel Gating
  • Humans
  • HEK293 Cells
 

Citation

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Yin, Y., Wu, M., Hsu, A. L., Borschel, W. F., Borgnia, M. J., Lander, G. C., & Lee, S.-Y. (2019). Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel. Nat Commun, 10(1), 3740. https://doi.org/10.1038/s41467-019-11733-5
Yin, Ying, Mengyu Wu, Allen L. Hsu, William F. Borschel, Mario J. Borgnia, Gabriel C. Lander, and Seok-Yong Lee. “Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel.Nat Commun 10, no. 1 (August 20, 2019): 3740. https://doi.org/10.1038/s41467-019-11733-5.
Yin Y, Wu M, Hsu AL, Borschel WF, Borgnia MJ, Lander GC, et al. Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel. Nat Commun. 2019 Aug 20;10(1):3740.
Yin, Ying, et al. “Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel.Nat Commun, vol. 10, no. 1, Aug. 2019, p. 3740. Pubmed, doi:10.1038/s41467-019-11733-5.
Yin Y, Wu M, Hsu AL, Borschel WF, Borgnia MJ, Lander GC, Lee S-Y. Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel. Nat Commun. 2019 Aug 20;10(1):3740.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 20, 2019

Volume

10

Issue

1

Start / End Page

3740

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • TRPM Cation Channels
  • Spodoptera
  • Sf9 Cells
  • Protein Structure, Quaternary
  • Patch-Clamp Techniques
  • Ion Channel Gating
  • Humans
  • HEK293 Cells