8JXR

Structure of nanobody-bound DRD1_LSD complex

8JXR の概要

• エントリーDOI: 10.2210/pdb8jxr/pdb
• EMDBエントリー: 36710
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: D(1A) dopamine receptor, NBA3, Maltose/maltodextrin-binding periplasmic protein,Immunoglobulin G-binding protein A,Immunoglobulin G-binding protein G, ... (7 entities in total)
• 機能のキーワード: gpcr, drd1, lsd, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 167637.48

構造登録者

Zhuang, Y.,Xu, Y.,Fan, L.,Wang, S.,Xu, H.E. (登録日: 2023-07-01, 公開日: 2024-09-04, 最終更新日: 2024-10-30)

主引用文献

Fan, L.,Zhuang, Y.,Wu, H.,Li, H.,Xu, Y.,Wang, Y.,He, L.,Wang, S.,Chen, Z.,Cheng, J.,Xu, H.E.,Wang, S.
Structural basis of psychedelic LSD recognition at dopamine D 1 receptor.
Neuron, 112:3295-, 2024

PubMed Abstract: Understanding the kinetics of LSD in receptors and subsequent induced signaling is crucial for comprehending both the psychoactive and therapeutic effects of LSD. Despite extensive research on LSD's interactions with serotonin 2A and 2B receptors, its behavior on other targets, including dopamine receptors, has remained elusive. Here, we present cryo-EM structures of LSD/PF6142-bound dopamine D receptor (DRD1)-legobody complexes, accompanied by a β-arrestin-mimicking nanobody, NBA3, shedding light on the determinants of G protein coupling versus β-arrestin coupling. Structural analysis unveils a distinctive binding mode of LSD in DRD1, particularly with the ergoline moiety oriented toward TM4. Kinetic investigations uncover an exceptionally rapid dissociation rate of LSD in DRD1, attributed to the flexibility of extracellular loop 2 (ECL2). Moreover, G protein can stabilize ECL2 conformation, leading to a significant slowdown in ligand's dissociation rate. These findings establish a solid foundation for further exploration of G protein-coupled receptor (GPCR) dynamics and their relevance to signal transduction.

PubMed: 39094559
DOI: 10.1016/j.neuron.2024.07.003

実験手法

ELECTRON MICROSCOPY (3.57 Å)