Structure and function of the photoreceptor rod cell
(in collaboration with Krzysztof Palczewski, Case Western Reserve University, Cleveland, USA).
The structural definition of components in GPCR-mediated signaling has progressed remarkably in the last 10 years, including structures of heterotrimeric and small molecular weight G proteins, modulators of G protein mediated signaling as well as structures of GPCRs in active and inactive states. Still lacking is a structural system-wide understanding of the signaling proteins and their interactions. The visual system represents an ideal target for this systems-wide analysis as it is well characterized structurally, biophysically and biochemically. Vertebrate visual phototransduction is one of the best-characterized GPCR mediated signaling pathways, and structural analyses of rhodopsin (Rho), transducin (Gt), arrestin and several other phototransduction components have revealed common folds and motifs important for its function. Although a wealth of static and dynamic information on Rho has been acquired by X-ray diffraction, solution and solid-state nuclear magnetic resonance spectroscopy, structural mass spectroscopy, electron and atomic force microscopy and a host of other biochemical and biophysical methods, the structural changes leading to the single photon detection capacity of photoreceptor rod cell still need to be unraveled. We will contribute to this by analyzing the Rho-Gt heteropentamer by electron crystallography.