Journal Article

Crystal structure of the channelrhodopsin light-gated cation channel

Hirata, Kunio, Deisseroth, Karl, Nureki, Osamu, Nishizawa, Tomohiro, Ishitani, Ryuichiro, Hegemann, Peter, Ramakrishnan, Charu, Tsukazaki, Tomoya, Yizhar, Ofer, Maturana, Andrés D., Kato, Hideaki E., Ito, Jumpei, Hayashi, Shigehiko, Zhang, Feng, Aita, Yusuke

2012

Overview

Channelrhodopsins (ChRs) are light-gated cation channels derived from algae that have shown experimental utility in optogenetics; for example, neurons expressing ChRs can be optically controlled with high temporal precision within systems as complex as freely moving mammals. Although ChRs have been broadly applied to neuroscience research, little is known about the molecular mechanisms by which these unusual and powerful proteins operate. Here we present the crystal structure of a ChR (a C1C2 chimaera between ChR1 and ChR2 from Chlamydomonas reinhardtii ) at 2.3 Å resolution. The structure reveals the essential molecular architecture of ChRs, including the retinal-binding pocket and cation conduction pathway. This integration of structural and electrophysiological analyses provides insight into the molecular basis for the remarkable function of ChRs, and paves the way for the precise and principled design of ChR variants with novel properties. Channelrhodopsins are light-gated cation channels used in optogenetics; here, the high-resolution crystal structure of a channelrhodopsin from Chlamydomonas reinhardtii is determined. Structure of key optogenetics reagent The channelrhodopsins are light-gated ion channels, found in algae, that have rapidly become familiar in the neuroscience lab as optogenetics reagents: the activities of neurons expressing channelrhodopsins can be optically controlled within systems as complicated as living mammals. The X-ray crystal structure of a chimaera of two channelrhodopsins has now been determined at 2.3 Å resolution. The structure reveals the molecular architecture of this ion channel, including the retinal-binding pocket and cation conduction pathway. This work paves the way for the design of new channelrhodopsin variants with enhanced properties.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/45/269 / 631/45/535 / Algae / Amino acids / Analytical, structural and metabolic biochemistry / Animals / Bacteriorhodopsins - chemistry / Binding Sites / Biological and medical sciences / Cations - metabolism / Cattle / Chlamydomonas reinhardtii / Chlamydomonas reinhardtii - chemistry / Chlamydomonas reinhardtii - genetics / Crystalline structure / Crystallography, X-Ray / Design / Fundamental and applied biological sciences. Psychology / Humanities and Social Sciences / Ion Channel Gating - radiation effects / Ion Channels - chemistry / Ion Channels - genetics / Ion Channels - radiation effects / Light / Models, Molecular / Molecular and cellular biology / Molecular biophysics / multidisciplinary / Mutation / Protein Conformation / Proteins / Recombinant Fusion Proteins - chemistry / Recombinant Fusion Proteins - genetics / Recombinant Fusion Proteins - radiation effects / Retinaldehyde - metabolism / Rhodopsin - chemistry / Rhodopsin - genetics / Rhodopsin - radiation effects / Schiff Bases - chemistry / Science / Science (multidisciplinary) / Signal transduction / Static Electricity / Structure in molecular biology