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TitleVisualizing structural transitions of ligand-dependent gating of the TRPM2 channel.
Journal, issue, pagesNat Commun, Vol. 10, Issue 1, Page 3740, Year 2019
Publish dateAug 20, 2019
AuthorsYing Yin / Mengyu Wu / Allen L Hsu / William F Borschel / Mario J Borgnia / Gabriel C Lander / Seok-Yong Lee /
PubMed AbstractThe 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 ...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.
External linksNat Commun / PubMed:31431622 / PubMed Central
MethodsEM (single particle)
Resolution3.8 - 4.5 Å
Structure data

20367

6pkv

EMDB-20367, PDB-6pkv:
Cryo-EM structure of the zebrafish TRPM2 channel in the apo conformation, processed with C4 symmetry
Method: EM (single particle) / Resolution: 4.3 Å

20368

6pkw

EMDB-20368, PDB-6pkw:
Cryo-EM structure of the zebrafish TRPM2 channel in the apo conformation, processed with C2 symmetry (pseudo C4 symmetry)
Method: EM (single particle) / Resolution: 4.5 Å

20369

6pkx

EMDB-20369, PDB-6pkx:
Cryo-EM structure of the zebrafish TRPM2 channel in the presence of ADPR and Ca2+
Method: EM (single particle) / Resolution: 4.2 Å

7822

6d73

EMDB-7822, PDB-6d73:
Cryo-EM structure of the zebrafish TRPM2 channel in the presence of Ca2+
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-AR6:
[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL

Source
  • danio rerio (zebrafish)
KeywordsTRANSPORT PROTEIN / warmth sensor / redox sensor / calcium-permeable ion channel / ion channel / TRP channel / TRPM channel / ADP-ribose

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