6PKX

Cryo-EM structure of the zebrafish TRPM2 channel in the presence of ADPR and Ca2+

Summary for 6PKX

• Entry DOI: 10.2210/pdb6pkx/pdb
• EMDB information: 20367 20368 20369
• Descriptor: Transient receptor potential cation channel subfamily M member 2, CALCIUM ION, [(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL [HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL] HYDROGEN PHOSPHATE (3 entities in total)
• Functional Keywords: warmth sensor, redox sensor, calcium-permeable ion channel, trp channel, trpm channel, ion channel, adp-ribose, transport protein
• Biological source: Danio rerio (Zebrafish)
• Total number of polymer chains: 4
• Total formula weight: 671633.29

Authors

Yin, Y.,Wu, M.,Hsu, A.L.,Borschel, W.F.,Borgnia, M.J.,Lander, G.C.,Lee, S.-Y. (deposition date: 2019-06-30, release date: 2019-08-28, Last modification date: 2024-10-30)

Primary citation

Yin, Y.,Wu, M.,Hsu, A.L.,Borschel, W.F.,Borgnia, M.J.,Lander, G.C.,Lee, S.Y.
Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel.
Nat Commun, 10:3740-3740, 2019

PubMed 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 Ca. The recently published TRPM2 structures from Danio rerio in the ligand-free and the ADPR/Ca-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 Ca alone, and with both ADPR and Ca, 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.

PubMed: 31431622
DOI: 10.1038/s41467-019-11733-5

Experimental method

ELECTRON MICROSCOPY (4.2 Å)