IDENTIFYING A PUTATIVE COMMON BINDING-SITE SHARED BY SUBSTANCE-P RECEPTOR AND AN ANTI-SUBSTANCE-P MONOCLONAL-ANTIBODY

Substance P G-protein coupled receptor and the antigen recognition site of a monoclonal antibody raised against substance P share a stretch of five contiguous identical amino acids, This observation prompted us to build an atomic model of both the receptor and the antibody and to analyse their common features, In particular, we report here that a pocket of similar size and composition is present in both proteins, strongly suggesting a similarity in the mode of binding of both macromolecules to substance P, From the analysis of our models, the available data on the mode of binding of the antibody to substance P and recent data on substance P receptor mutants, we concluded that the pocket is very likely to be involved in binding of the C-terminal 'message sequence' of the tachykinin. This allowed us to suggest specific site-directed mutants of the receptor which should shed some light on the mechanism of peptide recognition by G-protein coupled receptors.