Molecular Insights into Variable Electron Transfer in Amphibian Cryptochrome

Emil Sjulstok, Gesa Lüdemann, Tomáš Kubař, Marcus Elstner, Ilia A. Solov'yov
Biophysical Journal
Cryptochrome proteins are activated by the absorption of blue light, leading to the formation of radical pairsthrough electron transfer in the active site. Recent experimental studies have shown that once some of the amino acid residues
in the active site of Xenopus laevis cryptochrome DASH are mutated, radical-pair formation is still observed. In this study, we
computationally investigate electron-transfer pathways in the X. laevis cryptochrome DASH by extensively equilibrating a previously
established homology model using molecular dynamics simulations and then mutating key amino acids involved in the
electron transfer. The electron-transfer pathways are then probed by using tight-binding density-functional theory. We report the
alternative electron-transfer pathways resolved at the molecular level and, through comparison of amino acid sequences for
cryptochromes from different species, we demonstrate that one of these alternative electron-transfer pathways could be general
for all cryptochrome DASH proteins.