PMC:4504005 / 21157-21983 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4504005","sourcedb":"PMC","sourceid":"4504005","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4504005","text":"To explore the contribution of RAMP binding site augmentation to selectivity, we constructed RAMP “swap” mutants in which the four variable residue positions near the peptide C termini were reciprocally exchanged between RAMP1 and RAMP2 (A70/R97, W74/E101, F83/G110, and W84/F111) and we tested their response to CGRP and AM in the cAMP assay (Figures 6C and 6D). The clearest effect was one of a modest decrease in cognate ligand potency. Accordingly, CGRP potency decreased ∼10-fold at the CGRP receptor that included the RAMP1 mutant with RAMP2 residues and AM potency decreased ∼50-fold in the AM1 receptor with the RAMP2 mutant that contained RAMP1 residues. Thus, swapping these RAMP residues was insufficient to exchange pharmacological profiles, but the differing RAMP1/2 positions probably complicated the experiment.","tracks":[]}