Cryo-EM reveals a new allosteric binding site at the M₅ mAChR.

ABSTRACT: The M₅ muscarinic acetylcholine receptor (M₅ mAChR) represents a promising therapeutic target for neurological disorders. However, the high conservation of its orthosteric binding site has posed significant challenges for drug development. While selective positive allosteric modulators (PAMs) offer a potential solution, a structural understanding of the M₅ mAChR and its allosteric binding sites has remained limited. Here, we present a 2.8 Å cryo-electron microscopy structure of the M₅ mAChR complexed with heterotrimeric G_q protein and the agonist iperoxo, completing the active-state structural characterization of the mAChR family. To identify the binding site of M₅-selective PAMs, we implemented an integrated approach combin

SUBMITTER: Burger WAC 

PROVIDER: S-EPMC11838558 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature