DATE2024.09.04 #Press Releases
Elucidation of the High-light-sensitivity Mechanism of the Non-canonical Channelrhodopsin GtCCR4
Summary
A team led by Professor Osamu Nureki at the University of Tokyo and a team led by Professor Hideki Kandori at the Nagoya Institute of Technology have determined the cryo-EM structures of the channelrhodopsins GtCCR2 and GtCCR4. GtCCRs are cation channelrhodopsins from cryptophytes, first reported in 2016. These GtCCRs are evolutionarily distant from canonical channelrhodopsins, such as channelrhodopsin-2 from green algae, and are instead non-canonical channelrhodopsins with the same motif as the proton pump bacteriorhodopsin. Among them, GtCCR4 has 10-fold higher light sensitivity than GtCCR1-3 and channelrhodopsin-2, and it is being investigated as a novel optogenetic tool and gene therapy agent for blindness patients. However, it remains unclear how GtCCR4 achieves such high light sensitivity. In this study, the cryo-EM structures of GtCCR2 and GtCCR4 were reported. Moreover, electrophysiological and spectroscopic experiments elucidated the mechanism behind GtCCR4's high light sensitivity. These results suggest that the bend of transmembrane helix 6 in GtCCR4 shortens the channel recovery time and contributes to its high light sensitivity. Additionally, a comprehensive evaluation of the optogenetic properties and the creation of highly active mutants revealed the strong potential of GtCCR4 as an optogenetic tool. This study contributes to the development of more sensitive optogenetic tools and gene therapy agents for retinitis pigmentosa.
Figure：Cryo-EM maps of GtCCR2 and GtCCR4
Links：Nagoya Institute of Technology
Journals
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Journal name Molecular Cell Title of paper