Molecular mechanism of human α_1A-adrenoceptor inhibition by Mamba snake toxin AdTx1.

ABSTRACT: There is growing interest in peptide or small protein based drugs targeting G protein-coupled receptors (GPCRs) for improved subtype selectivity over small molecules. Naturally occurring toxins represent rich sources of such ligands. AdTx1 (ρ-Da1a), a three-finger toxin (3FTx) from the green Mamba Snake, selectively binds and antagonizes α-adrenoceptors. Here, we present the cryo-electron microscopy structure of α_1A-adrenoceptor in complex with AdTx1. The structure reveals the molecular mechanism of the subtype selectivity and antagonist activity of AdTx1 for α_1A-adrenoceptor, which is different from those revealed by the only 3FTx-GPCR structure reported so far, the Muscarinic toxins 7 (MT7) - Muscarinic acetylcholine receptor 1 (M₁AChR) structure. Based o

SUBMITTER: Shi M 

PROVIDER: S-EPMC12267694 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature