Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein.

ABSTRACT: Inhibition of calcitonin gene-related peptide (CGRP) or its cognate CGRP receptor (CGRPR) has arisen as a major breakthrough in the treatment of migraine. However, a second CGRP-responsive receptor exists, the amylin (Amy) 1 receptor (AMY₁R), yet its involvement in the pathology of migraine is poorly understood. AMY₁R and CGRPR are heterodimers consisting of receptor activity-modifying protein 1 (RAMP1) with the calcitonin receptor (CTR) and the calcitonin receptor-like receptor (CLR), respectively. Here, we present the structure of AMY₁R in complex with CGRP and Gs protein and compare it with the reported structures of the AMY₁R complex with rat amylin (rAmy) and the CGRPR in complex with CGRP. Despite similar protein backbones observed within t

SUBMITTER: Cao J 

PROVIDER: S-EPMC11080994 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature