| Research Abstract |
One of the motifs of signal transduction systems widely present in organisms is the [Receptor→G protein→Enzyme]. The receptor (G protein-coupled receptor, GPCR) which participates in this system has seven-transmembrane α-helical structure, and 2000 or more kinds are discovered so far.
GPCR have been variously diversified in the course of molecular evolution, and they support organisms working as sophisticated information processing systems. In the present study, we have investigated the functional expression of GPCR using a rhodopsin as a model GPCR for furthering our understanding of the common mechanism of G protein activation by GPCR and its diversification.
Consequently, it was revealed that the fundamental molecular architectures for activating G protein are similar among GPCRs belonging to a rhodopsin super family (family 1). On the other hand, comparison of rhodopsin with metabotropic glutamate receptor (mGluR) suggested that the molecular architectures of rhodopsin and mGluR related to G protein interaction are different but the G protein activation mechanism involving the cytoplasmic loops is common. Moreover, the structural changes of rhodopsin in the process from photoreception to G protein activation were investigated by means of various spectroscopic and molecular biological techniques. Consequently, it was elucidated the mechanism of helical movements induced by the light-activated retinal chromophore, and identified the amino acid residues which control the rate of structural changes in rhodopsin molecule.
Furthermore, the three-dimensional structure of rhodopsin was explored and seven water molecules were identified in the molecule. It was also found that the counterion which are important for absorption of a visible light have been diversified among the groups of rhodopsin family.
|
