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Nat Commun. 2018 May 24;9(1):2046. doi: 10.1038/s41467-018-04428-w.

Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain.

Author information

1
Institute for Biology, Experimental Biophysics, Humboldt-Universität zu Berlin, 10115, Berlin, Germany.
2
Institute for Synaptic Physiology, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany.
3
Department of Biology, Institute for Molecular Plant Physiology and Biophysics, Biocenter, Julius-Maximilians-University of Würzburg, Julius-von-Sachs-Platz 2, 97082, Würzburg, Germany.
4
Institute for Synaptic Physiology, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, 20251, Hamburg, Germany. christine.gee@zmnh.uni-hamburg.de.
5
Institute for Biology, Experimental Biophysics, Humboldt-Universität zu Berlin, 10115, Berlin, Germany. hegemann@rz.hu-berlin.de.

Abstract

The cyclic nucleotides cAMP and cGMP are important second messengers that orchestrate fundamental cellular responses. Here, we present the characterization of the rhodopsin-guanylyl cyclase from Catenaria anguillulae (CaRhGC), which produces cGMP in response to green light with a light to dark activity ratio >1000. After light excitation the putative signaling state forms with τ = 31 ms and decays with τ = 570 ms. Mutations (up to 6) within the nucleotide binding site generate rhodopsin-adenylyl cyclases (CaRhACs) of which the double mutated YFP-CaRhAC (E497K/C566D) is the most suitable for rapid cAMP production in neurons. Furthermore, the crystal structure of the ligand-bound AC domain (2.25 Å) reveals detailed information about the nucleotide binding mode within this recently discovered class of enzyme rhodopsin. Both YFP-CaRhGC and YFP-CaRhAC are favorable optogenetic tools for non-invasive, cell-selective, and spatio-temporally precise modulation of cAMP/cGMP with light.

PMID:
29799525
PMCID:
PMC5967339
DOI:
10.1038/s41467-018-04428-w
[Indexed for MEDLINE]
Free PMC Article

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