QuasAr Odyssey: the origin of fluorescence and its voltage sensitivity in microbial rhodopsins

作者：Arita Silapētere, Songhwan Hwang, Yusaku Hontani, Rodrigo Gaston Fernandez Lahore, Jens Balke, Francisco Vélazquez Escobar, Martijn Tros, Patrick E. Konold, Rainer Matis, Roberta Croce, Peter Jomo Walla, Peter Hildebrandt, Ulrike Alexiev, John T. M. Kennis, Han Sun, Tillmann Utesch, Peter Hegemann · 发表于：Nature Communications · 年份：2022 · DOI：10.1038/s41467-022-33084-4 · 被引用次数：31 · 研究领域：Photoreceptor and optogenetics research、Molecular Communication and Nanonetworks、Neural dynamics and brain function

Rhodopsins had long been considered non-fluorescent until a peculiar voltage-sensitive fluorescence was reported for archaerhodopsin-3 (Arch3) derivatives. These proteins named QuasArs have been used for imaging membrane voltage changes in cell cultures and small animals, but they could not be applied in living rodents. To develop the next generation of sensors, it is indispensable to first understand the molecular basis of the fluorescence and its modulation by the membrane voltage. Based on spectroscopic studies of fluorescent Arch3 derivatives, we propose a unique photo-reaction scheme with extended excited-state lifetimes and inefficient photoisomerization. Molecular dynamics simulations of Arch3, of the Arch3 fluorescent derivative Archon1, and of several its mutants have revealed different voltage-dependent changes of the hydrogen-bonding networks including the protonated retinal Schiff-base and adjacent residues. Experimental observations suggest that under negative voltage, these changes modulate retinal Schiff base deprotonation and promote a decrease in the populations of fluorescent species. Finally, we identified molecular constraints that further improve fluorescence quantum yield and voltage sensitivity.