Mutational Study of the Tryptophan Tetrad Important for Electron Transfer in European Robin Cryptochrome 4a

The ability of migratory birds to sense magnetic fieldshas beenknown for decades, although the understanding of the underlying mechanismis still elusive. Currently, the strongest magnetoreceptor candidatein birds is a protein called cryptochrome 4a. The cryptochrome 4aprotein has changed through evolution, apparently endowing some birdswith a more pronounced magnetic sensitivity than others. Using phylogenetictools, we show that a specific tryptophan tetrad and a tyrosine residuepredicted to be essential for cryptochrome activation are highly conservedin the avian clade. Through state-of-the-art molecular dynamics simulationsand associated analyses, we also studied the role of these specificresidues and the associated mutants on the overall dynamics of theprotein. The analyses of the single residue mutations were used tojudge how far a local change in the protein structure can impact specificdynamics of European robin cryptochrome 4a. We conclude that the replacementsof each of the tryptophans one by one with a phenylalanine do notcompromise the overall stability of the protein.