PUBLICATION
Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel
- Authors
- Yin, Y., Wu, M., Hsu, A.L., Borschel, W.F., Borgnia, M.J., Lander, G.C., Lee, S.Y.
- ID
- ZDB-PUB-190822-3
- Date
- 2019
- Source
- Nature communications 10: 3740 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adenosine Diphosphate Ribose/metabolism*
- Cell Line
- TRPM Cation Channels/metabolism*
- Sf9 Cells
- Humans
- Spodoptera
- Zebrafish
- Patch-Clamp Techniques
- Cryoelectron Microscopy
- Protein Structure, Quaternary*
- Ion Channel Gating
- Animals
- Calcium/metabolism*
- HEK293 Cells
- PubMed
- 31431622 Full text @ Nat. Commun.
Citation
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. Nature communications. 10:3740.
Abstract
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.
Genes / Markers
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Human Disease / Model
Sequence Targeting Reagents
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