Sunlight is the driving force behind all biological processes on earth. To synchronize their biological clocks with the natural day-night cycle, most living things rely on photosensitive proteins called cryptochromes. In this work, the research group of Prof. Manuel Maestre-Reyes, a faculty member of the Department of Chemistry, NTU, utilized time-resolved serial femtosecond crystallography to film a 3D molecular movie of cryptochrome photoreception and subsequent structural changes from 10 ns to 233 ms after illumination.
This movie (see below) explains how, after photoreception, the cryptochrome acts as a signal amplifier, with fast and subtle structural changes in the flavin adenine dinucleotide (FAD) chromophore inducing slow, dramatic structural transitions. During the initial photochemical change, FAD was photoreduced by the protein. The resulting radical pair (FAD•–/Y373• RP) activated three distinct protein regions: the FAD binding site, the transient protonation pathway (TPP) and helix α22, which is close to Y373.
Nanoseconds after illumination, the FAD binding site stabilized the RP by hydrogen bonding FAD•–. This hydrogen bond switch also activated the TPP within microseconds, which extended the RP life into the millisecond time-scale by delivering a proton to the FAD•– radical. Finally, after several milliseconds, the enduring presence of Y373• near helix α22 caused the latter to unfold like a ribbon, an unmistakable and easily detectable signal of cryptochrome having sensed light.
These results give unprecedented insight into the principles of light-triggered processes in nature. In addition, charge separation via transient RP formation is central to oxidative phosphorylation, photosynthesis, and even biomagnetosensitivity. Thus, the cryptochrome molecular mechanism may act as a model system to better understand the fundamentals of these central topics in biophysical chemistry.
Contact Details:
- Prof. Dr. Manuel Maestre-Reyna
- Department of Chemistry, National Taiwan University
- E-mail: mmaestre@ntu.edu.tw