Structures, Dynamics and Photochemistry of Novel Photoreceptors

Photoreceptors are signaling proteins that perceive light signals and convert them into biological signals that regulate a wide range of physiological processes. Several photoreceptor proteins have been applied to synthetic biology and cell imaging for biomedical research and optogenetics applications. My dissertation work has been focused on structural studies on two distinct novel photoreceptors from cyanobacteria: orange carotenoid protein (OCP) and a bilin-based far-red light photoreceptor. First, orange carotenoid protein is a blue light photoreceptor involved in the protection of the photosynthetic reaction apparatuses in cyanobacteria under high light conditions. We were able to directly observe the light-induced structural changes of OCP at atomic resolution using dynamic crystallography, which suggests a new type of photochemistry exploited by biological systems. Second, the far-red absorbing cyanobacteriochromes (FR-CBCRs) belong to a recently discovered family of bilin-based photoreceptors. Since these modular and compact FR-CBCRs display the action spectra in the far-red light region that overlaps with the therapeutic optical window, they are highly desirable for optogenetics and deep tissue imaging. We have determined the first crystal structure for the FR-CBCR family, which reveals highly unusual structural features in the chromophore and protein moiety. These structural findings, together with site-directed mutagenesis, provide mechanistic insights into the far-red spectral tuning and photoconversion in bilin-based photoreceptors.