Mapping G protein coupling domains by site-specific peptides

This chapter discusses mapping G protein coupling domains by site-specific peptides. Transmembrane signaling pathways, in general, require a signal transduction coupling mechanism to link external signals to cellular responses. More specifically, G protein-coupled receptors (GPCRs) make use of regulatory guanosine nucleotide binding proteins to transmit stimulation of the receptor by the first messenger (hormone, neurotransmitter, and agonist) to the effector (enzyme or ion channel). In all consecutive steps, the signal is transmitted by coupling through protein–protein interactions. If two proteins interact, it appears reasonable that small peptides derived from the putative polypeptide contact domains might be true substitutes or competitors of the larger entities making them useful tools to study the specific properties of the interaction. Mapping G protein coupling domains by site-specific peptides provides the means to establish a functional topography of receptor interaction sites. Receptors that act via G proteins share substantial structural homology, including rhodopsin, which, by its similarity to bacteriorhodopsin, provides the only structural model at the molecular level.