7V3Z

Structure of cannabinoid receptor type 1(CB1)

Summary for 7V3Z

• Entry DOI: 10.2210/pdb7v3z/pdb
• Descriptor: fusion protein of Cannabinoid receptor 1 and Flavodoxin, 2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol, CHOLESTEROL, ... (4 entities in total)
• Functional Keywords: activation, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 49822.16

Authors

Liu, Z.J.,Shen, L.,Hua, T.,Yao, D.Q.,Wu, L.J. (deposition date: 2021-08-12, release date: 2021-11-24, Last modification date: 2024-10-09)

Primary citation

Wang, X.,Liu, D.,Shen, L.,Li, F.,Li, Y.,Yang, L.,Xu, T.,Tao, H.,Yao, D.,Wu, L.,Hirata, K.,Bohn, L.M.,Makriyannis, A.,Liu, X.,Hua, T.,Liu, Z.J.,Wang, J.
A Genetically Encoded F-19 NMR Probe Reveals the Allosteric Modulation Mechanism of Cannabinoid Receptor 1.
J.Am.Chem.Soc., 143:16320-16325, 2021

PubMed Abstract: Due to the lack of genetically encoded probes for fluorine-19 nuclear magnetic resonance spectroscopy (F NMR), its utility for probing eukaryotic membrane protein dynamics is limited. Here we report an efficient method for the genetic incorporation of an unnatural amino acid (UAA), 3'-trifluoromenthyl-phenylalanine (mtfF), into cannabinoid receptor 1 (CB1) in the Baculovirus Expression System. The probe can be inserted at any environmentally sensitive site, while causing minimal structural perturbation to the target protein. Using F NMR and X-ray crystallography methods, we discovered that the allosteric modulator Org27569 and agonists synergistically stabilize a previously unrecognized pre-active state. An allosteric modulation model is proposed to explain Org27569's distinct behavior. We demonstrate that our site-specific F NMR labeling method is a powerful tool in decoding the mechanism of GPCR allosteric modulation. This new method should be broadly applicable for uncovering conformational states for many important eukaryotic membrane proteins.

PubMed: 34596399
DOI: 10.1021/jacs.1c06847

Experimental method

X-RAY DIFFRACTION (3.29 Å)