title: Extended Electron-Transfer in Animal Cryptochromes Mediated by a Tetrad of Aromatic Amino Acids.
abstract: The cryptochrome/photolyase protein family possesses a conserved triad of tryptophans that may act as a molecular wire to transport electrons from the protein surface to the FAD cofactor for activation and/or signaling-state formation. Members from the animal (and animal-like) cryptochrome subclade use this process in a light-induced fashion in a number of exciting responses, such as the (re-)setting of circadian rhythms or magnetoreception; however, electron-transfer pathways have not been explored in detail yet. Therefore, we present an in-depth time-resolved optical and electron-paramagnetic resonance spectroscopic study of two cryptochromes from Chlamydomonas reinhardtii and Drosophila melanogaster. The results do not only reveal the existence of a fourth, more distant aromatic amino acid that serves as a terminal electron donor in both proteins, but also show that a tyrosine is able to fulfill this very role in Chlamydomonas reinhardtii cryptochrome. Additionally, exchange of the respective fourth aromatic amino acid to redox-inactive phenylalanines still leads to light-induced radical pair formation; however, the lifetimes of these species are drastically reduced from the ms- to the μs-range. The results presented in this study open up a new chapter, to our knowledge, in the diversity of electron-transfer pathways in cryptochromes. Moreover, they could explain unique functions of animal cryptochromes, in particular their potential roles in magnetoreception because magnetic-field effects of light-induced radical pairs strongly depend on distance and orientation parameters.
authors.affiliation: Institute of Physical Chemistry, University of Freiburg, Freiburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nohr
authors.affiliation: University of Marburg, Marburg, Germany.
authors.forename: Sophie
authors.initials: S
authors.lastname: Franz
authors.affiliation: Institute of Physical Chemistry, University of Freiburg, Freiburg, Germany.
authors.forename: Ryan
authors.initials: R
authors.lastname: Rodriguez
authors.affiliation: Institute of Physical Chemistry, University of Freiburg, Freiburg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Paulus
authors.affiliation: University of Marburg, Marburg, Germany. Electronic address: essen@chemie.uni-marburg.de.
authors.forename: Lars-Oliver
authors.initials: LO
authors.lastname: Essen
authors.affiliation: Institute of Physical Chemistry, University of Freiburg, Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weber
authors.affiliation: Institute of Physical Chemistry, University of Freiburg, Freiburg, Germany. Electronic address: erik.schleicher@physchem.uni-freiburg.de.
authors.forename: Erik
authors.initials: E
authors.lastname: Schleicher
mesh_terms: D024322:Amino Acids, Aromatic / Q000378:metabolism*; D000818:Animals; D016825:Chlamydomonas reinhardtii; D056931:Cryptochromes / Q000737:chemistry* / Q000378:metabolism*; D004331:Drosophila melanogaster; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D024322:Amino Acids, Aromatic; D056931:Cryptochromes