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Structure paper

TitleChannelrhodopsins with distinct chromophores and binding patterns.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 7292, Year 2024
Publish dateAug 24, 2024
AuthorsYuanyue Shan / Liping Zhao / Meiyu Chen / Xiao Li / Mingfeng Zhang / Duanqing Pei /
PubMed AbstractChannelrhodopsins are popular optogenetic tools in neuroscience, but remain poorly understood mechanistically. Here we report the cryo-EM structures of channelrhodopsin-2 (ChR2) from Chlamydomonas ...Channelrhodopsins are popular optogenetic tools in neuroscience, but remain poorly understood mechanistically. Here we report the cryo-EM structures of channelrhodopsin-2 (ChR2) from Chlamydomonas reinhardtii and H. catenoides kalium channelrhodopsin (KCR1). We show that ChR2 recruits an endogenous N-retinylidene-PE-like molecule to a previously unidentified lateral retinal binding pocket, exhibiting a reduced light response in HEK293 cells. In contrast, H. catenoides kalium channelrhodopsin (KCR1) binds an endogenous retinal in its canonical retinal binding pocket under identical condition. However, exogenous ATR reduces the photocurrent magnitude of wild type KCR1 and also inhibits its leaky mutant C110T. Our results uncover diverse retinal chromophores with distinct binding patterns for channelrhodopsins in mammalian cells, which may further inspire next generation optogenetics for complex tasks such as cell fate control.
External linksNat Commun / PubMed:39181878 / PubMed Central
MethodsEM (single particle)
Resolution2.4 - 2.6 Å
Structure data

39880

8zam

EMDB-39880, PDB-8zam:
EndoChR2 channelrhodopsin
Method: EM (single particle) / Resolution: 2.5 Å

39881

8zan

EMDB-39881, PDB-8zan:
ExoChR2 channelrhodopsin
Method: EM (single particle) / Resolution: 2.4 Å

39882

8zao

EMDB-39882, PDB-8zao:
ExoKCR1 channelrhodopsin
Method: EM (single particle) / Resolution: 2.6 Å

39883

8zap

EMDB-39883, PDB-8zap:
ExoC110T class 1 channelrhodopsin
Method: EM (single particle) / Resolution: 2.6 Å

39884

8zaq

EMDB-39884, PDB-8zaq:
ExoC110T class 2 channelrhodopsin
Method: EM (single particle) / Resolution: 2.6 Å

Chemicals

ChemComp-L9Q:
(1S)-2-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-1-[(octadecanoyloxy)methyl]ethyl (9Z)-octadec-9-enoate

ChemComp-RET:
RETINAL

ChemComp-K:
Unknown entry

ChemComp-HOH:
WATER

Source
  • chlamydomonas reinhardtii (plant)
  • hyphochytrium catenoides (eukaryote)
KeywordsMEMBRANE PROTEIN / Channelrhodopsin

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