6MXT

Crystal structure of human beta2 adrenergic receptor bound to salmeterol and Nb71

「6CSY」から置き換えられました

6MXT の概要

• エントリーDOI: 10.2210/pdb6mxt/pdb
• 分子名称: Endolysin, Beta-2 adrenergic receptor chimera, nanobody Nb71, salmeterol, ... (10 entities in total)
• 機能のキーワード: g protein-coupled receptor, adrenergic receptor, asthma drug, active conformation, nanobody, signaling protein-hormone complex, membrane protein, signaling protein/hormone
• 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: 68731.36

構造登録者

Masureel, M.,Zou, Y.,Picard, L.P.,van der Westhuizen, E.,Mahoney, J.P.,Rodrigues, J.P.G.L.M.,Mildorf, T.J.,Dror, R.O.,Shaw, D.E.,Bouvier, M.,Pardon, E.,Steyaert, J.,Sunahara, R.K.,Weis, W.I.,Zhang, C.,Kobilka, B.K. (登録日: 2018-10-31, 公開日: 2018-11-14, 最終更新日: 2023-10-11)

主引用文献

Masureel, M.,Zou, Y.,Picard, L.P.,van der Westhuizen, E.,Mahoney, J.P.,Rodrigues, J.P.G.L.M.,Mildorf, T.J.,Dror, R.O.,Shaw, D.E.,Bouvier, M.,Pardon, E.,Steyaert, J.,Sunahara, R.K.,Weis, W.I.,Zhang, C.,Kobilka, B.K.
Structural insights into binding specificity, efficacy and bias of a beta2AR partial agonist.
Nat. Chem. Biol., 14:1059-1066, 2018

PubMed Abstract: Salmeterol is a partial agonist for the β adrenergic receptor (βAR) and the first long-acting βAR agonist to be widely used clinically for the treatment of asthma and chronic obstructive pulmonary disease. Salmeterol's safety and mechanism of action have both been controversial. To understand its unusual pharmacological action and partial agonism, we obtained the crystal structure of salmeterol-bound βAR in complex with an active-state-stabilizing nanobody. The structure reveals the location of the salmeterol exosite, where sequence differences between βAR and βAR explain the high receptor-subtype selectivity. A structural comparison with the βAR bound to the full agonist epinephrine reveals differences in the hydrogen-bond network involving residues Ser204 and Asn293. Mutagenesis and biophysical studies suggested that these interactions lead to a distinct active-state conformation that is responsible for the partial efficacy of G-protein activation and the limited β-arrestin recruitment for salmeterol.

PubMed: 30327561
DOI: 10.1038/s41589-018-0145-x

実験手法

X-RAY DIFFRACTION (2.95934213525 Å)