Receptor activity-modifying protein-dependent effects of mutations in the calcitonin receptor-like receptor: implications for adrenomedullin and calcitonin gene-related peptide pharmacology.

ABSTRACT:

Background and purpose

Receptor activity-modifying proteins (RAMPs) define the pharmacology of the calcitonin receptor-like receptor (CLR). The interactions of the different RAMPs with this class B GPCR yield high-affinity calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors. However, the mechanism for this is unclear.

Experimental approach

Guided by receptor models, we mutated residues in the N-terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions. These were assayed for cAMP production with AM, AM2 and CGRP together with their cell surface expression. Binding studies were also conducted for selected mutants.

Key results

An important domain for peptide interactions on CLR from I32 to I52 was defined. Although I4

SUBMITTER: Watkins HA 

PROVIDER: S-EPMC3969088 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature