7BTS

Structure of human beta1 adrenergic receptor bound to epinephrine and nanobody 6B9

Summary for 7BTS

• Entry DOI: 10.2210/pdb7bts/pdb
• Descriptor: Lysozyme-Beta-1 adrenergic receptor chimera, Camelid Antibody Fragment, L-EPINEPHRINE, ... (8 entities in total)
• Functional Keywords: g protein coupled receptor, membrane protein
• Biological source: Enterobacteria phage T4; More
• Total number of polymer chains: 2
• Total formula weight: 66893.22

Authors

Xu, X.,Kaindl, J.,Clark, M.,Hubner, H.,Hirata, K.,Sunahara, R.,Gmeiner, P.,Kobilka, B.K.,Liu, X. (deposition date: 2020-04-02, release date: 2020-12-02, Last modification date: 2024-10-30)

Primary citation

Xu, X.,Kaindl, J.,Clark, M.J.,Hubner, H.,Hirata, K.,Sunahara, R.K.,Gmeiner, P.,Kobilka, B.K.,Liu, X.
Binding pathway determines norepinephrine selectivity for the human beta 1 AR over beta 2 AR.
Cell Res., 31:569-579, 2021

PubMed Abstract: Beta adrenergic receptors (βARs) mediate physiologic responses to the catecholamines epinephrine and norepinephrine released by the sympathetic nervous system. While the hormone epinephrine binds βAR and βAR with similar affinity, the smaller neurotransmitter norepinephrine is approximately tenfold selective for the βAR. To understand the structural basis for this physiologically important selectivity, we solved the crystal structures of the human βAR bound to an antagonist carazolol and different agonists including norepinephrine, epinephrine and BI-167107. Structural comparison revealed that the catecholamine-binding pockets are identical between βAR and βAR, but the extracellular vestibules have different shapes and electrostatic properties. Metadynamics simulations and mutagenesis studies revealed that these differences influence the path norepinephrine takes to the orthosteric pocket and contribute to the different association rates and thus different affinities.

PubMed: 33093660
DOI: 10.1038/s41422-020-00424-2

Experimental method

X-RAY DIFFRACTION (3.13 Å)