6CSO

Crystal structure of the designed light-gated anion channel iC++ at pH6.5

Summary for 6CSO

• Entry DOI: 10.2210/pdb6cso/pdb
• Descriptor: iC++, RETINAL, OLEIC ACID (3 entities in total)
• Functional Keywords: rhodopsin, channelrhodopsin, anion channel, optogenetics, membrane protein
• Biological source: Chlamydomonas reinhardtii
• Total number of polymer chains: 1
• Total formula weight: 35130.94

Authors

Kato, H.E.,Kim, Y.,Yamashita, K.,Kobilka, B.K.,Deisseroth, K. (deposition date: 2018-03-21, release date: 2018-09-05, Last modification date: 2023-10-04)

Primary citation

Kato, H.E.,Kim, Y.S.,Paggi, J.M.,Evans, K.E.,Allen, W.E.,Richardson, C.,Inoue, K.,Ito, S.,Ramakrishnan, C.,Fenno, L.E.,Yamashita, K.,Hilger, D.,Lee, S.Y.,Berndt, A.,Shen, K.,Kandori, H.,Dror, R.O.,Kobilka, B.K.,Deisseroth, K.
Structural mechanisms of selectivity and gating in anion channelrhodopsins.
Nature, 561:349-354, 2018

PubMed Abstract: Both designed and natural anion-conducting channelrhodopsins (dACRs and nACRs, respectively) have been widely applied in optogenetics (enabling selective inhibition of target-cell activity during animal behaviour studies), but each class exhibits performance limitations, underscoring trade-offs in channel structure-function relationships. Therefore, molecular and structural insights into dACRs and nACRs will be critical not only for understanding the fundamental mechanisms of these light-gated anion channels, but also to create next-generation optogenetic tools. Here we report crystal structures of the dACR iC++, along with spectroscopic, electrophysiological and computational analyses that provide unexpected insights into pH dependence, substrate recognition, channel gating and ion selectivity of both dACRs and nACRs. These results enabled us to create an anion-conducting channelrhodopsin integrating the key features of large photocurrent and fast kinetics alongside exclusive anion selectivity.

PubMed: 30158697
DOI: 10.1038/s41586-018-0504-5

Experimental method

X-RAY DIFFRACTION (3.2 Å)