7BTS

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

7BTS の概要

• エントリーDOI: 10.2210/pdb7bts/pdb
• 分子名称: Lysozyme-Beta-1 adrenergic receptor chimera, Camelid Antibody Fragment, L-EPINEPHRINE, ... (8 entities in total)
• 機能のキーワード: g protein coupled receptor, membrane protein
• 由来する生物種: Enterobacteria phage T4; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66893.22

構造登録者

Xu, X.,Kaindl, J.,Clark, M.,Hubner, H.,Hirata, K.,Sunahara, R.,Gmeiner, P.,Kobilka, B.K.,Liu, X. (登録日: 2020-04-02, 公開日: 2020-12-02, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.13 Å)