Channelrhodopsin unchained: Structure and mechanism of a light-gated cation channel |
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Authors: | Ví ctor A. Ló renz-Fonfrí a,Joachim Heberle |
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Affiliation: | Freie Universität Berlin, Experimental Molecular Biophysics, Arnimallee 14, 14195 Berlin, Germany |
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Abstract: | The new and vibrant field of optogenetics was founded by the seminal discovery of channelrhodopsin, the first light-gated cation channel. Despite the numerous applications that have revolutionised neurophysiology, the functional mechanism is far from understood on the molecular level. An arsenal of biophysical techniques has been established in the last decades of research on microbial rhodopsins. However, application of these techniques is hampered by the duration and the complexity of the photoreaction of channelrhodopsin compared with other microbial rhodopsins. A particular interest in resolving the molecular mechanism lies in the structural changes that lead to channel opening and closure. Here, we review the current structural and mechanistic knowledge that has been accomplished by integrating the static structure provided by X-ray crystallography and electron microscopy with time-resolved spectroscopic and electrophysiological techniques. The dynamical reactions of the chromophore are effectively coupled to structural changes of the protein, as shown by ultrafast spectroscopy. The hierarchical sequence of structural changes in the protein backbone that spans the time range from 10− 12 s to 10− 3 s prepares the channel to open and, consequently, cations can pass. Proton transfer reactions that are associated with channel gating have been resolved. In particular, glutamate 253 and aspartic acid 156 were identified as proton acceptor and donor to the retinal Schiff base. The reprotonation of the latter is the critical determinant for channel closure. The proton pathway that eventually leads to proton pumping is also discussed. This article is part of a Special Issue entitled: Retinal Proteins — You can teach an old dog new tricks. |
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Keywords: | ASR, Anabaena sensory rhodopsin BHK cells, baby hamster kidney cells bR, H. salinarum bacteriorhodopsin CaChR, Chlamydomonas augustae channelrhodopsin ChR, channelrhodopsin ChR1, ChR1 from Chlamydomonas reinhardtii ChR2, ChR2 from Chlamydomonas reinhardtii C1C2, ChR1&ndash ChR2 chimaera CyChR, Chlamydomonas yellowstonensis channelrhodopsin DsChR, Dunaliella salina channelrhodopsin FTIR, Fourier transform infrared HeLa cells, Henrietta Lacks cells HEK cells, human embryonic kidney cells hR, H. salinarum halorhodopsin MD, molecular dynamics MM, molecular mechanics MvChR, Mesostigma viride ChR QM, quantum mechanics SB, Schiff base sRII, sensory rhodopsin II VcChR, Volvox carteri ChR YFP, yellow fluorescent protein |
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