Prediction of interfaces For Gpcr Oligomer

摘要

About 1000 genes encoding GPCRs (G protein Coupled Receptors) exist in human genome. Because over 30% of clinically marketed drugs are active at this family, GPCRs are one of the most important target classes of proteins for drug. For the last fifteen years, the formation of GPCR homo and hetero oligomer has been suggested by biochemical and pharmacological evidence. More recently, by atomic force microscopy, it was revealed that bovine rhodopsins form a homo oligomer in native membrane [2]. Some subtypes form oligomers, while others do not. The oligomerization patterns differ with the subtypes of GPCRs. Signal transduction by GPCRs are considered to be associated with the oligomerization. To clarify the mechanism of signal transduction, it is important to elucidate the oligomeric patterns of GPCRs. Accordingly, prediction of interface for the oligomerization would be the first step to understand the mechanism of the oligomerization. When we examined the spatial distribution of highly conserved residues in the structure of bovine rhodopsin, significantly large number of highly conserved residues are observed at the oligomeric interface. Based on the observation, we tried to develop a method to predict the interface for the-GPCR oligomers.