RT Journal Article
SR Electronic
T1 Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 516468
DO 10.1101/516468
A1 Ying Yin
A1 Mengyu Wu
A1 Allen L. Hsu
A1 William F. Borschel
A1 Mario J. Borgnia
A1 Gabriel C. Lander
A1 Seok-Yong Lee
YR 2019
UL http://biorxiv.org/content/early/2019/01/09/516468.abstract
AB The calcium-permeable transient receptor potential melastatin 2 (TRPM2) channel plays a key role in redox sensation in many cell types 1–3. Channel activation requires binding of both ADP-ribose (ADPR) 2,4–6 and Ca2+ 7. The recently published TRPM2 structures from Danio rerio in the ligand-free and in the ADPR/Ca2+-bound conditions represent the channel in closed and open states, which uncover substantial tertiary and quaternary conformational rearrangements 8. However, it is unclear how these rearrangements occur within the tetrameric channel during channel gating. Here we report two cryo-electron microscopy structures of TRPM2 from the same species in complex with Ca2+ alone, and with both ADPR and Ca2+, determined to an overall resolution of ~3.8 Å and ~4.2 Å respectively. In comparison with the published results, our studies capture TRPM2 in two-fold symmetric intermediate states, offering a glimpse of the structural transitions within the tetramer that bridge the closed and open conformations.