Human Calcitonin and Amylin receptor HDX-MS

ABSTRACT: Receptor activity-modifying proteins (RAMPs) regulate the pharmacology, trafficking, and signaling of class B1 G protein-coupled receptors (GPCRs). The calcitonin receptor (CTR) interacts with each of the three RAMPs to form amylin receptors (AMYRs), which display distinct ligand preferences and signaling outputs. While cryo-electron microscopy has described AMYR structures in active conformations, less is known about how RAMPs influence CTR dynamics in the absence of ligand. In this study, we applied hydrogen–deuterium exchange mass spectrometry (HDX-MS) to examine conformational dynamics of the CTR alone and in complex with RAMP1, RAMP2, or RAMP3 in their apo states. The data show that RAMPs alter the flexibility of several CTR regions, including extracellular loops, transmembrane helices, and intracellular segments associated with G protein binding. In addition, each RAMP subtype displays characteristic dynamic features within its transmembrane and C-terminal domains. These HDX-MS datasets provide mechanistic insight into how RAMPs modulate CTR structure and offer a resource that links static structural models with functional pharmacology.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Tracy Josephs  

LAB HEAD: Tracy Maree Josephs

PROVIDER: PXD068848 | Pride | 2026-06-08

REPOSITORIES: Pride