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Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs.

<div class='caption-title'>Structure of ChRmine in lipid nanodiscs.</div>
<div class='caption-title'>A lipid-filled central pore in ChRmine.</div>
<div class='caption-title'>The ChRmine ion conduction pathway.</div>
Tucker K, Sridharan S, Adesnik H, Brohawn SG
OpenAccess logo Nat Commun 13 4842 (2022)
Related entries: 7sfk, 7shs

Cited: 9 times
EuropePMC logo PMID: 35977941

Abstract

Microbial channelrhodopsins are light-gated ion channels widely used for optogenetic manipulation of neuronal activity. ChRmine is a bacteriorhodopsin-like cation channelrhodopsin (BCCR) more closely related to ion pump rhodopsins than other channelrhodopsins. ChRmine displays unique properties favorable for optogenetics including high light sensitivity, a broad, red-shifted activation spectrum, cation selectivity, and large photocurrents, while its slow closing kinetics impedes some applications. The structural basis for ChRmine function, or that of any other BCCR, is unknown. Here, we present cryo-EM structures of ChRmine in lipid nanodiscs in apo (opsin) and retinal-bound (rhodopsin) forms. The structures reveal an unprecedented trimeric architecture with a lipid filled central pore. Large electronegative cavities on either side of the membrane facilitate high conductance and selectivity for cations over protons. The retinal binding pocket structure suggests channel properties could be tuned with mutations and we identify ChRmine variants with ten-fold decreased and two-fold increased closing rates. A T119A mutant shows favorable properties relative to wild-type and previously reported ChRmine variants for optogenetics. These results provide insight into structural features that generate an ultra-potent microbial opsin and provide a platform for rational engineering of channelrhodopsins with improved properties that could expand the scale, depth, and precision of optogenetic experiments.

Articles - 7sfj mentioned but not cited (1)

  1. Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs. Tucker K, Sridharan S, Adesnik H, Brohawn SG. Nat Commun 13 4842 (2022)


Reviews citing this publication (1)

  1. Microbial circadian clocks: host-microbe interplay in diel cycles. Wollmuth EM, Angert ER. BMC Microbiol 23 124 (2023)

Articles citing this publication (7)

  1. Kalium channelrhodopsins are natural light-gated potassium channels that mediate optogenetic inhibition. Govorunova EG, Gou Y, Sineshchekov OA, Li H, Lu X, Wang Y, Brown LS, St-Pierre F, Xue M, Spudich JL. Nat Neurosci 25 967-974 (2022)
  2. WiChR, a highly potassium-selective channelrhodopsin for low-light one- and two-photon inhibition of excitable cells. Vierock J, Peter E, Grimm C, Rozenberg A, Chen IW, Tillert L, Castro Scalise AG, Casini M, Augustin S, Tanese D, Forget BC, Peyronnet R, Schneider-Warme F, Emiliani V, Béjà O, Hegemann P. Sci Adv 8 eadd7729 (2022)
  3. LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins. Ansell TB, Song W, Coupland CE, Carrique L, Corey RA, Duncan AL, Cassidy CK, Geurts MMG, Rasmussen T, Ward AB, Siebold C, Stansfeld PJ, Sansom MSP. Nat Commun 14 7774 (2023)
  4. Structural Foundations of Potassium Selectivity in Channelrhodopsins. Govorunova EG, Sineshchekov OA, Brown LS, Bondar AN, Spudich JL. mBio 13 e0303922 (2022)
  5. Structural basis for ion selectivity in potassium-selective channelrhodopsins. Tajima S, Kim YS, Fukuda M, Jo Y, Wang PY, Paggi JM, Inoue M, Byrne EFX, Kishi KE, Nakamura S, Ramakrishnan C, Takaramoto S, Nagata T, Konno M, Sugiura M, Katayama K, Matsui TE, Yamashita K, Kim S, Ikeda H, Kim J, Kandori H, Dror RO, Inoue K, Deisseroth K, Kato HE. Cell 186 4325-4344.e26 (2023)
  6. A light-gated cation channel with high reactivity to weak light. Hososhima S, Ueno S, Okado S, Inoue KI, Konno M, Yamauchi Y, Inoue K, Terasaki H, Kandori H, Tsunoda SP. Sci Rep 13 7625 (2023)
  7. Structures of channelrhodopsin paralogs in peptidiscs explain their contrasting K+ and Na+ selectivities. Morizumi T, Kim K, Li H, Govorunova EG, Sineshchekov OA, Wang Y, Zheng L, Bertalan É, Bondar AN, Askari A, Brown LS, Spudich JL, Ernst OP. Nat Commun 14 4365 (2023)


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