Immunological approaches for probing receptor structure and function.

Abstract

Molecular cloning has revealed the primary sequence of numerous membrane receptors, and this information catalysed two important efforts: modeling of receptor structure by hydropathy analysis and generating sequence-specific immunological probes with which these models can be tested experimentally. Craig Malbon and his colleagues outline the recent advances that illustrate how anti-peptide antibodies raised to synthetic sequences of membrane receptor have generated new information on the topology, functional domains and cellular localization of transmembrane signaling elements. They focus on two examples, the G protein-linked beta-adrenoceptor, and the nicotinic acetylcholine receptor, an intrinsic ion channel receptor. These two classes of receptor provide templates for the analysis of topographical models of membrane proteins with immunological probes, especially anti-peptide antibodies, and demonstrate how these results complement those obtained from molecular, biochemical and biophysical techniques. Although this powerful strategy is not without faults, it is likely to continue to be applied successfully to the analysis of the structure and function of receptors, ion channels and other membrane proteins.