Structural insight into ligand binding and activation of the orphan GPCR Mas1
Yumu Zhang·H Eric Xu·Heng Liu·Hong Shan·Yimin Gu·Jiaqi Yang·Yuan Gao·Keyu Wu·Dehua Yang·Qiuying Wang
Abstract The Mas1 receptor, an orphan class A G-protein-coupled receptor (GPCR), plays pivotal roles in cardiovascular and anti-inflammatory regulation. Despite its therapeutic relevance, the structural mechanisms underlying Mas1 ligand binding and activation remain poorly understood. Here, we report cryo-EM structures of Mas1 bound to two chemically distinct agonists—neuropeptide FF (NPFF) and synthetic small-molecule AR234958—captured in complex with inhibitory G proteins. These structures rev