ABSTRACT
The search for novel GPCRs in a genome of interest is confounded by issues arising from the complex nature of multigene families, splice variants, and polymorphisms where numerous variant forms or alleles of a single gene exist within the population. Therefore, reliable, experimentally verifi ed functional annotation of GPCR genes is problematic. Moreover, the protein complement of a cell (proteome) is considerably larger and in many ways much more complex than the genome because the number of proteins encoded by the human genome are far greater in number than the number of genes. Posttranslational modifi cations, cleavage of precursors, and other types of proteolytic modifi cations may magnify this number even further. Thus, identifying, cataloguing, and characterizing the GPCR complement of the human proteome in the near future will prove signifi cantly more challenging than annotation of the genome. With this in mind, in this chapter we describe existing status of various dimensions of GPCR structural and functional characterizations and some new strategies that may open new avenues to rational drug design and discovery.
