6N4B

Cannabinoid Receptor 1-G Protein Complex

Summary for 6N4B

• Entry DOI: 10.2210/pdb6n4b/pdb
• EMDB information: 0339
• Descriptor: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (7 entities in total)
• Functional Keywords: cannabinoid receptor, gpcr, synthetic cannabinoid, fubinaca, gi, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 170581.46

Authors

Krishna Kumar, K.,Shalev-Benami, M.,Hu, H.,Weis, W.I.,Kobilka, B.K.,Skiniotis, G. (deposition date: 2018-11-18, release date: 2019-01-30, Last modification date: 2024-10-09)

Primary citation

Krishna Kumar, K.,Shalev-Benami, M.,Robertson, M.J.,Hu, H.,Banister, S.D.,Hollingsworth, S.A.,Latorraca, N.R.,Kato, H.E.,Hilger, D.,Maeda, S.,Weis, W.I.,Farrens, D.L.,Dror, R.O.,Malhotra, S.V.,Kobilka, B.K.,Skiniotis, G.
Structure of a Signaling Cannabinoid Receptor 1-G Protein Complex.
Cell, 176:448-, 2019

PubMed Abstract: Cannabis elicits its mood-enhancing and analgesic effects through the cannabinoid receptor 1 (CB1), a G protein-coupled receptor (GPCR) that signals primarily through the adenylyl cyclase-inhibiting heterotrimeric G protein G. Activation of CB1-G signaling pathways holds potential for treating a number of neurological disorders and is thus crucial to understand the mechanism of G activation by CB1. Here, we present the structure of the CB1-G signaling complex bound to the highly potent agonist MDMB-Fubinaca (FUB), a recently emerged illicit synthetic cannabinoid infused in street drugs that have been associated with numerous overdoses and fatalities. The structure illustrates how FUB stabilizes the receptor in an active state to facilitate nucleotide exchange in G. The results compose the structural framework to explain CB1 activation by different classes of ligands and provide insights into the G protein coupling and selectivity mechanisms adopted by the receptor.

PubMed: 30639101
DOI: 10.1016/j.cell.2018.11.040

Experimental method

ELECTRON MICROSCOPY (3 Å)