6H7M

ACTIVATED TURKEY BETA1 ADRENOCEPTOR WITH BOUND PARTIAL AGONIST SALBUTAMOL AND NANOBODY Nb6B9

Summary for 6H7M

• Entry DOI: 10.2210/pdb6h7m/pdb
• Descriptor: Thioredoxin 1, Beta-1 adrenergic receptor, Camelid antibody fragment Nb6B9, ... (7 entities in total)
• Functional Keywords: beta1 adrenoceptor, activated, partial agonist, nanobody, immune system
• Biological source: Escherichia coli (strain K12); More
• Total number of polymer chains: 6
• Total formula weight: 122828.23

Authors

Warne, T.,Edwards, P.C.,Dore, A.S.,Leslie, A.G.W.,Tate, C.G. (deposition date: 2018-07-31, release date: 2018-10-17, Last modification date: 2024-01-17)

Primary citation

Warne, T.,Edwards, P.C.,Dore, A.S.,Leslie, A.G.W.,Tate, C.G.
Molecular basis for high-affinity agonist binding in GPCRs.
Science, 364:775-778, 2019

PubMed 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 β-adrenoceptor (βAR) bound to conformation-specific nanobodies in the presence of agonists of varying efficacy. Comparison with inactive-state structures of βAR 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.

PubMed: 31072904
DOI: 10.1126/science.aau5595

Experimental method

X-RAY DIFFRACTION (2.76 Å)