Far-Red Absorbing Rhodopsins, Insights From Heterodimeric Rhodopsin-Cyclases

Abstract

The recently discovered Rhodopsin-cyclases from Chytridiomycota fungi show completely unexpected properties for microbial rhodopsins. These photoreceptors function exclusively as heterodimers, with the two subunits that have very different retinal chromophores. Among them is the bimodal photoswitchable Neorhodopsin (NeoR), which exhibits a near-infrared absorbing, highly fluorescent state. These are features that have never been described for any retinal photoreceptor. Here these properties are discussed in the context of color-tuning approaches of retinal chromophores, which have been extensively studied since the discovery of the first microbial rhodopsin, bacteriorhodopsin, in 1971 (Oesterhelt et al., Nature New Biology, 1971, 233 (39), 149–152). Further a brief review about the concept of heterodimerization is given, which is widely present in class III cyclases but is unknown for rhodopsins. NIR-sensitive retinal chromophores have greatly expanded our understanding of the spectral range of natural retinal photoreceptors and provide a novel perspective for the development of optogenetic tools.

Rhodopsins: An Excitingly Versatile Protein Species for Research, Development and Creative Engineering

“…While bacteriorhodopsin is the dominant photoreceptor in Halobacterium salinarum , this archaeon eventually turned out to harbour several related photosensitive proteins, both with ion transport and sensory functions ( Oesterhelt, 1998 ). Since the 1990s this field exploded, with more strains, including eukaryotic organisms like algae and fungi, and other functionalities being revealed every year ( Béjà et al, 2000 ; Spudich et al, 2000 ; Brown, 2004 ; Rozenberg et al, 2021 ; Broser, 2022 ; Nagata and Inoue, 2022 ). More recently even viral rhodopsins have been discovered ( Philosof and Béjà, 2013 ; Bratanov et al, 2019 ; Zabelskii et al, 2020 ).…”

“…Circular dichroism spectroscopy provides evidence for exciton coupling between the chromophores ( Cassim, 1992 ; Fujimoto and Inoue, 2020 ; Fujimoto, 2021 ). For eukaryotic type-1 rhodopsins, homo-dimeric as well as hetero-dimeric complexes are observed ( Mukherjee et al, 2019 ; Govorunova et al, 2021 ; Broser, 2022 ). Isolated type-1 monomers are also functionally active, indicating that the oligomeric assembly probably affords optimal packing and mutual stabilization, and/or the opportunity to modulate monomer activity by inter-subunit interplay ( Iizuka et al, 2019 ).…”

“…Overall, type-1 pigments are the dominant contributors to marine phototrophy ( Casey et al, 2017 ; Larkum et al, 2018 ; Gómez-Consarnau et al, 2019 ). In addition, eukaryotic type-1 rhodopsins have been discovered which are intracellularly fused to an enzymatic domain and mediate light-driven enzyme activation (guanylyl cyclase, phosphodiesterase) or inhibition (guanylyl cyclase, based upon histidine kinase activity) ( Avelar et al, 2014 ; Lamarche et al, 2017 ; Luck et al, 2019 ; Mukherjee et al, 2019 ; Tsunoda et al, 2021 ; Broser, 2022 ; Tian et al, 2022 ). These pigments have been termed as enzyme-rhodopsins.…”

“…Rapid spectroscopy has been performed on quite a number of type-1 pigments, and the global scheme is quite similar to that of bacteriorhodopsin ( Figure 8C ). However, the kinetics of the slower steps (M and subsequent ones) and thereby the overall cycle time can vary considerably from ms up to minutes ( Rozenberg et al, 2021 ; Tsunoda et al, 2021 ; Broser, 2022 ; Nagata and Inoue, 2022 ).…”

“…A large number of excellent reviews on the rhodopsin families have been published, many of which we have referred to where appropriate, along with the most relevant early and recent papers. We refrain from presenting many molecular details, and therefore we refer to the following more recent reviews ( DeGrip and Rothschild, 2000 ; Hofmann, 2000 ; Spudich et al, 2000 ; Hofmann et al, 2009 ; Yizhar et al, 2011 ; Palczewski and Orban, 2013 ; Ernst et al, 2014 ; Imamoto and Shichida, 2014 ; Inoue et al, 2014 ; Deisseroth, 2015 ; Hofmann and Palczewski, 2015 ; Brown and Ernst, 2017 ; Bando et al, 2019 ; El Khatib and Atamian, 2019 ; Dowling, 2020 ; Kandori, 2020 ; Kwon et al, 2020 ; Baillie et al, 2021 ; Moraes et al, 2021 ; Rozenberg et al, 2021 ; Bondar, 2022 ; Broser, 2022 ; Brown, 2022 ; Khelashvili and Menon, 2022 ; Nagata and Inoue, 2022 ).…”