Ligand-Specific Allosteric Coupling Controls G-Protein-Coupled Receptor Signaling.

ABSTRACT: Allosteric coupling describes a reciprocal process whereby G-protein-coupled receptors (GPCRs) relay ligand-induced conformational changes from the extracellular binding pocket to the intracellular signaling surface. Therefore, GPCR activation is sensitive to both the type of extracellular ligand and intracellular signaling protein. We hypothesized that ligand-specific allosteric coupling may result in preferential (i.e., biased) engagement of downstream effectors. However, the structural basis underlying ligand-dependent control of this essential allosteric mechanism is poorly understood. Here, we show that two sets of extended muscarinic acetylcholine receptor M₁ agonists, which only differ in linker length, progressively constrain receptor signaling. We demonstrate that stepw

SUBMITTER: Holze J 

PROVIDER: S-EPMC7551708 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature