PDBsum entry 6h7m

Immune system

PDB id: 6h7m

Contents

Protein chains

107 a.a.

291 a.a.

120 a.a.

Ligands

2CV ×7

68H ×2

Metals

_NA ×2

Waters ×13

References listed in PDB file

Key reference

• Title: Molecular basis for high-Affinity agonist binding in gpcrs.
• Authors: T.Warne, P.C.Edwards, A.S.Doré, A.G.W.Leslie, C.G.Tate.
• Ref.: Science, 2019, 364, 775-778. [DOI no: 10.1126/science.aau5595]
• PubMed id: 31072904

Abstract

G protein-coupled receptors (GPCRs) in the G protein-coupled active state have higher affinity for agonists as compared with when they are in the inactive state, but the molecular basis for this is unclear. We have determined four active-state structures of the β₁-adrenoceptor (β₁AR) bound to conformation-specific nanobodies in the presence of agonists of varying efficacy. Comparison with inactive-state structures of β₁AR bound to the identical ligands showed a 24 to 42% reduction in the volume of the orthosteric binding site. Potential hydrogen bonds were also shorter, and there was up to a 30% increase in the number of atomic contacts between the receptor and ligand. This explains the increase in agonist affinity of GPCRs in the active state for a wide range of structurally distinct agonists.