ORCID Profile
0000-0001-5379-2951
Current Organisation
University of Tokyo
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Publisher: Cold Spring Harbor Laboratory
Date: 15-08-2021
DOI: 10.1101/2021.08.15.456392
Abstract: ChRmine 1 , a recently-discovered bacteriorhodopsin-like cation-conducting channelrhodopsin 1, 2 , exhibits puzzling properties (unusually-large photocurrents, exceptional red-shift in action spectrum, and extreme light-sensitivity) that have opened up new opportunities in optogenetics 1, 3–5 . ChRmine and its homologs function as light-gated ion channels, but by primary sequence more closely resemble ion pump rhodopsins the molecular mechanisms for passive channel conduction in this family of proteins, as well as the unusual properties of ChRmine itself, have remained mysterious. Here we present the cryo-electron microscopy structure of ChRmine at 2.0 Å resolution. The structure reveals striking architectural features never seen before in channelrhodopsins including trimeric assembly, a short transmembrane-helix 3 unwound in the middle of the membrane, a prominently-twisting extracellular-loop 1, remarkably-large intracellular cavities and extracellular vestibule, and an unprecedented hydrophilic pore that extends through the center of the trimer, separate from the three in idual monomer pores. Electrophysiological, spectroscopic, and computational analyses provide insight into conduction and gating of light-gated channels with these distinct design features, and point the way toward structure-guided creation of novel channelrhodopsins for optogenetic applications in biology.
Publisher: Proceedings of the National Academy of Sciences
Date: 23-05-2018
Abstract: Complex photoreceptors have independently evolved in animals with radial and bilateral symmetry, but little is known about the proteins that transduce light information (opsins) in radially symmetrical animals. We use homology modeling and heterologous action spectroscopy to study the structure of an opsin (JellyOp) from the lens eye of the visually competent box jellyfish, Carybdea rastonii . We find that a key structural feature of animal opsins—the counterion—maintains visible-light sensitivity in JellyOp from a unique location, E94 in the transmembrane bundle. This unique position for the counterion, the third only discovered in animal opsins, closely mirrors the location in vertebrate visual proteins, which was thought to be a unique adaptation in vertebrates to achieve higher fidelity photoreception.
Publisher: Cold Spring Harbor Laboratory
Date: 31-10-2022
DOI: 10.1101/2022.10.30.514430
Abstract: The KCR channelrhodopsins are recently-discovered light-gated ion channels with high K + selectivity, a property that has attracted broad attention among biologists– due to intense interest in creating novel inhibitory tools for optogenetics leveraging this K + selectivity, and due to the mystery of how this selectivity is achieved in the first place. Indeed, the molecular and structural mechanism for K + selectivity in KCRs has remained especially puzzling since these 7-transmembrane retinal-binding proteins completely lack structural similarity with known K + channels, which generally coordinate K + in a precisely symmetric conduction pathway formed by a tight interface among multiple small monomeric channel subunits (presumably not an accessible mechanism for the large KCR rhodopsin proteins). Here we present the cryo-electron microscopy structures of two KCRs from Hyphochytrium catenoides with distinct spectral properties for light absorption and channel actuation, Hc KCR1, and Hc KCR2, at resolutions of 2.6 and 2.5 Å, respectively. Structural comparison revealed first an unusually-shaped retinal binding pocket which induces rotation of the retinal in Hc KCR2, explaining the large spectral difference between Hc KCR1 and 2. Next, our combined structural, electrophysiological, computational, and spectroscopic analyses revealed a new solution to the challenging problem of K + -selective transport. KCRs indeed do not exhibit the canonical tetrameric K + selectivity filter that specifically coordinates dehydrated K + instead, single KCR monomers form a size exclusion filter using aromatic residues at the extracellular side of the pore which inhibits passage of bulky hydrated ions. This unique feature allows KCRs to function as K + channels under relevant physiological conditions, providing not only a novel mechanism for achieving high K + permeability ratios in biological ion channels, but also a framework for designing the next generation of inhibitory optogenetic tools. The first structures of K + -selective channelrhodopsins ( Hc KCR1 and 2) are determined, revealing a K + selectivity mechanism distinctly different from canonical K + channels. The cryo-EM structures of K + -selective channelrhodopsins, Hc KCR1 and 2, in nanodisc Conditions under which naturally-occurring microbial rhodopsins have a 6-s- cis retinal Identification of key residues for high K + permeability ratios The unique K + selectivity mechanism of KCRs
Publisher: Elsevier BV
Date: 02-2022
No related grants have been discovered for Takashi Nagata.