Structure of a Signaling Cannabinoid Receptor 1-G Protein Complex

Kumar, Kaavya Krishna; Shalev-Benami, Moran; Robertson, Michael J.; Hu, Hongli; Banister, Samuel D.; Hollingsworth, Scott A.; Latorraca, Naomi R.; Kato, Hideaki E.; Hilger, Daniel; Maeda, Shoji; Weis, William I.; Farrens, David L.; Dror, Ron O.; Malhotra, Sanjay V.; Kobilka, Brian K.; Skiniotis, Georgios

doi:10.1016/j.cell.2018.11.040

Title: Structure of a Signaling Cannabinoid Receptor 1-G Protein Complex

Journal Article · 10 January 2019 · Cell

DOI: https://doi.org/10.1016/j.cell.2018.11.040 · OSTI ID:1503451

Kumar, Kaavya Krishna ^[1]; Shalev-Benami, Moran ^[1]; Robertson, Michael J. ^[1]; Hu, Hongli ^[1]; Banister, Samuel D. ^[1]; Hollingsworth, Scott A. ^[2]; Latorraca, Naomi R. ^[2]; Kato, Hideaki E. ^[1]; Hilger, Daniel ^[1]; Maeda, Shoji ^[1]; Weis, William I. ^[3]; Farrens, David L. ^[4]; Dror, Ron O. ^[2]; Malhotra, Sanjay V. ^[1]; Kobilka, Brian K. ^[1]; Skiniotis, Georgios ^[3]

Stanford Univ. School of Medicine, Stanford, CA (United States)
Stanford Univ. School of Medicine, Stanford, CA (United States); Stanford Univ., Stanford, CA (United States)
Stanford Univ. School of Medicine, Stanford, CA (United States); Stanford Univ., Menlo Park, CA (United States). SLAC National Accelerator Lab
Oregon Health Sciences Univ., Portland, OR (United States)

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_i. Activation of CB1-G_i signaling pathways holds potential for treating a number of neurological disorders and is thus crucial to understand the mechanism of G_i activation by CB1. Here, we present the structure of the CB1-G_i 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_i. Furthermore 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.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-76SF00515; R37DA036246; R01GM083118

OSTI ID:: 1503451

Journal Information:: Cell, Vol. 176, Issue 3; ISSN 0092-8674

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 247 works

Citation information provided by
Web of Science

References (78)

Guidelines for using Bsoft for high resolution reconstruction and validation of biomolecular structures from electron micrographs: Using Bsoft for Single Particle Reconstruction Heymann, J. Bernard Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3293	journal	October 2017
Routine single particle CryoEM sample and grid characterization by tomography Noble, Alex J.; Dandey, Venkata P.; Wei, Hui eLife, Vol. 7 https://doi.org/10.7554/eLife.34257	journal	May 2018
Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain: CB1 expression in murine forebrain Marsicano, Giovanni; Lutz, Beat European Journal of Neuroscience, Vol. 11, Issue 12 https://doi.org/10.1046/j.1460-9568.1999.00847.x	journal	December 1999
The influence of cannabinoids on generic traits of neurodegeneration: Cannabinoids and neurodegeneration Fagan, S. G.; Campbell, V. A. British Journal of Pharmacology, Vol. 171, Issue 6 https://doi.org/10.1111/bph.12492	journal	March 2014
CB1 cannabinoid receptor-mediated tyrosine phosphorylation of focal adhesion kinase-related non-kinase Zhou, Dan; Song, Z. H. FEBS Letters, Vol. 525, Issue 1-3 https://doi.org/10.1016/S0014-5793(02)03091-0	journal	July 2002
MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG Williams, Christopher J.; Headd, Jeffrey J.; Moriarty, Nigel W. Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3330	journal	November 2017
Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 2. Explicit Solvent Particle Mesh Ewald Salomon-Ferrer, Romelia; Götz, Andreas W.; Poole, Duncan Journal of Chemical Theory and Computation, Vol. 9, Issue 9 https://doi.org/10.1021/ct400314y	journal	August 2013
Endocannabinoid system and mood disorders: Priming a target for new therapies Micale, Vincenzo; Di Marzo, Vincenzo; Sulcova, Alexandra Pharmacology & Therapeutics, Vol. 138, Issue 1 https://doi.org/10.1016/j.pharmthera.2012.12.002	journal	April 2013
Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal Cooper, Ziva D. Current Psychiatry Reports, Vol. 18, Issue 5 https://doi.org/10.1007/s11920-016-0694-1	journal	April 2016
Structure of the adenosine-bound human adenosine A1 receptor–Gi complex Draper-Joyce, Christopher J.; Khoshouei, Maryam; Thal, David M. Nature, Vol. 558, Issue 7711 https://doi.org/10.1038/s41586-018-0236-6	journal	June 2018
The Structure–Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation Bow, Eric W.; Rimoldi, John M. Perspectives in Medicinal Chemistry, Vol. 8 https://doi.org/10.4137/PMC.S32171	journal	January 2016
The Dynamic Process of β2-Adrenergic Receptor Activation Nygaard, Rie; Zou, Yaozhong; Dror, Ron O. Cell, Vol. 152, Issue 3 https://doi.org/10.1016/j.cell.2013.01.008	journal	January 2013
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
Development of an antibody fragment that stabilizes GPCR/G-protein complexes Maeda, Shoji; Koehl, Antoine; Matile, Hugues Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-06002-w	journal	September 2018
Long-range corrected hybrid density functionals with damped atom–atom dispersion corrections Chai, Jeng-Da; Head-Gordon, Martin Physical Chemistry Chemical Physics, Vol. 10, Issue 44 https://doi.org/10.1039/b810189b	journal	January 2008
Opioid Receptor Signalling Mechanisms Connor, Mark; Christie, MacDonald J. Clinical and Experimental Pharmacology and Physiology, Vol. 26, Issue 7 https://doi.org/10.1046/j.1440-1681.1999.03049.x	journal	July 1999
The Cannabinoid Receptor CB1 Interacts with the WAVE1 Complex and Plays a Role in Actin Dynamics and Structural Plasticity in Neurons Njoo, Christian; Agarwal, Nitin; Lutz, Beat PLOS Biology, Vol. 13, Issue 10 https://doi.org/10.1371/journal.pbio.1002286	journal	October 2015
Formation of -/ -opioid receptor heterodimer is sex-dependent and mediates female-specific opioid analgesia Chakrabarti, S.; Liu, N. -J.; Gintzler, A. R. Proceedings of the National Academy of Sciences, Vol. 107, Issue 46 https://doi.org/10.1073/pnas.1009923107	journal	November 2010
Crystal Structure of the Human Cannabinoid Receptor CB1 Hua, Tian; Vemuri, Kiran; Pu, Mengchen Cell, Vol. 167, Issue 3 https://doi.org/10.1016/j.cell.2016.10.004	journal	October 2016
Structural flexibility of the G s -helical domain in the 2-adrenoceptor Gs complex Westfield, G. H.; Rasmussen, S. G. F.; Su, M. Proceedings of the National Academy of Sciences, Vol. 108, Issue 38 https://doi.org/10.1073/pnas.1113645108	journal	September 2011
Potential Control of Multiple Sclerosis by Cannabis and the Endocannabinoid System Pryce, Gareth; Baker, David CNS & Neurological Disorders - Drug Targets, Vol. 11, Issue 5 https://doi.org/10.2174/187152712801661310	journal	June 2012
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Mutation Studies of Ser7.39 and Ser2.60 in the Human CB ₁ Cannabinoid Receptor: Evidence for a Serine-Induced Bend in CB ₁ Transmembrane Helix 7 Kapur, Ankur; Hurst, Dow P.; Fleischer, Daniel Molecular Pharmacology, Vol. 71, Issue 6 https://doi.org/10.1124/mol.107.034645	journal	March 2007
Structural insights into µ-opioid receptor activation Huang, Weijiao; Manglik, Aashish; Venkatakrishnan, A. J. Nature, Vol. 524, Issue 7565 https://doi.org/10.1038/nature14886	journal	August 2015
Structural determinants in the second intracellular loop of the human cannabinoid CB1 receptor mediate selective coupling to Gs and Gi: Coupling of cannabinoid CB1 receptors to Gs and Gi Chen, Xp; Yang, W.; Fan, Y. British Journal of Pharmacology, Vol. 161, Issue 8 https://doi.org/10.1111/j.1476-5381.2010.01006.x	journal	November 2010
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors Ballesteros, Juan A.; Weinstein, Harel Receptor Molecular Biology, Vol. 25, p. 366-428 https://doi.org/10.1016/S1043-9471(05)80049-7	book	January 1995
Structural Basis of G Protein-coupled Receptor-Gi Protein Interaction Mnpotra, Jagjeet S.; Qiao, Zhuanhong; Cai, Jian Journal of Biological Chemistry, Vol. 289, Issue 29 https://doi.org/10.1074/jbc.M113.539916	journal	July 2014
“Zombie” Outbreak Caused by the Synthetic Cannabinoid AMB-FUBINACA in New York Adams, Axel J.; Banister, Samuel D.; Irizarry, Lisandro New England Journal of Medicine, Vol. 376, Issue 3 https://doi.org/10.1056/NEJMoa1610300	journal	January 2017
Molecular and Behavioral Pharmacological Characterization of Abused Synthetic Cannabinoids MMB- and MDMB-FUBINACA, MN-18, NNEI, CUMYL-PICA, and 5-Fluoro-CUMYL-PICA Gamage, Thomas F.; Farquhar, Charlotte E.; Lefever, Timothy W. Journal of Pharmacology and Experimental Therapeutics, Vol. 365, Issue 2 https://doi.org/10.1124/jpet.117.246983	journal	March 2018
JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB ₁ receptor agonist: ‘Spice’ contains a potent cannabinoid agonist Atwood, Brady K.; Huffman, John; Straiker, Alex British Journal of Pharmacology, Vol. 160, Issue 3 https://doi.org/10.1111/j.1476-5381.2009.00582.x	journal	January 2010
Cannabinoid Receptors as Therapeutic Targets Mackie, Ken Annual Review of Pharmacology and Toxicology, Vol. 46, Issue 1 https://doi.org/10.1146/annurev.pharmtox.46.120604.141254	journal	February 2006
Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go García-Nafría, Javier; Nehmé, Rony; Edwards, Patricia C. Nature, Vol. 558, Issue 7711 https://doi.org/10.1038/s41586-018-0241-9	journal	June 2018
A Structural Insight into the Reorientation of Transmembrane Domains 3 and 5 during Family A G Protein-Coupled Receptor Activation Sansuk, Kamonchanok; Deupi, Xavier; Torrecillas, Ivan R. Molecular Pharmacology, Vol. 79, Issue 2 https://doi.org/10.1124/mol.110.066068	journal	November 2010
High-resolution crystal structure of the human CB1 cannabinoid receptor Shao, Zhenhua; Yin, Jie; Chapman, Karen Nature, Vol. 540, Issue 7634 https://doi.org/10.1038/nature20613	journal	November 2016
Improved Peptide and Protein Torsional Energetics with the OPLS-AA Force Field Robertson, Michael J.; Tirado-Rives, Julian; Jorgensen, William L. Journal of Chemical Theory and Computation, Vol. 11, Issue 7 https://doi.org/10.1021/acs.jctc.5b00356	journal	June 2015
Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes Ryckaert, Jean-Paul; Ciccotti, Giovanni; Berendsen, Herman J. C. Journal of Computational Physics, Vol. 23, Issue 3 https://doi.org/10.1016/0021-9991(77)90098-5	journal	March 1977
Prediction of the Water Content in Protein Binding Sites Michel, Julien; Tirado-Rives, Julian; Jorgensen, William L. The Journal of Physical Chemistry B, Vol. 113, Issue 40 https://doi.org/10.1021/jp9047456	journal	October 2009
cisTEM, user-friendly software for single-particle image processing Grant, Timothy; Rohou, Alexis; Grigorieff, Nikolaus eLife, Vol. 7 https://doi.org/10.7554/eLife.35383	journal	March 2018
Single-molecule analysis of ligand efficacy in β2AR–G-protein activation Gregorio, G. Glenn; Masureel, Matthieu; Hilger, Daniel Nature, Vol. 547, Issue 7661 https://doi.org/10.1038/nature22354	journal	June 2017
Dual Effects of DAMGO [d-Ala ² , N -Me-Phe ⁴ ,Gly ⁵ -ol]-Enkephalin and CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH ₂ ) on Adenylyl Cyclase Activity: Implications for μ-Opioid Receptor G _s Coupling Szücs, Mária; Boda, Krisztina; Gintzler, Alan R. Journal of Pharmacology and Experimental Therapeutics, Vol. 310, Issue 1 https://doi.org/10.1124/jpet.104.066837	journal	March 2004
Insights into the Role of Asp79 ^2.50 in β ₂ Adrenergic Receptor Activation from Molecular Dynamics Simulations Ranganathan, Anirudh; Dror, Ron O.; Carlsson, Jens Biochemistry, Vol. 53, Issue 46 https://doi.org/10.1021/bi5008723	journal	November 2014
Cannabinoid Receptors and Their Endogenous Agonists Felder, Christian C.; Glass, Michelle Annual Review of Pharmacology and Toxicology, Vol. 38, Issue 1 https://doi.org/10.1146/annurev.pharmtox.38.1.179	journal	April 1998
Structure of the µ-opioid receptor–Gi protein complex Koehl, Antoine; Hu, Hongli; Maeda, Shoji Nature, Vol. 558, Issue 7711 https://doi.org/10.1038/s41586-018-0219-7	journal	June 2018
A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects Ignatowska-Jankowska, Bogna M.; Baillie, Gemma L.; Kinsey, Steven Neuropsychopharmacology, Vol. 40, Issue 13 https://doi.org/10.1038/npp.2015.148	journal	June 2015
Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb Izzo, Angelo A.; Borrelli, Francesca; Capasso, Raffaele Trends in Pharmacological Sciences, Vol. 30, Issue 10 https://doi.org/10.1016/j.tips.2009.07.006	journal	October 2009
CTFFIND4: Fast and accurate defocus estimation from electron micrographs Rohou, Alexis; Grigorieff, Nikolaus Journal of Structural Biology, Vol. 192, Issue 2 https://doi.org/10.1016/j.jsb.2015.08.008	journal	November 2015
Automation of the CHARMM General Force Field (CGenFF) I: Bond Perception and Atom Typing Vanommeslaeghe, K.; MacKerell, A. D. Journal of Chemical Information and Modeling, Vol. 52, Issue 12 https://doi.org/10.1021/ci300363c	journal	November 2012
The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins Lauckner, J. E.; Hille, B.; Mackie, K. Proceedings of the National Academy of Sciences, Vol. 102, Issue 52 https://doi.org/10.1073/pnas.0509588102	journal	December 2005
Relevance of rhodopsin studies for GPCR activation Deupi, Xavier Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1837, Issue 5 https://doi.org/10.1016/j.bbabio.2013.09.002	journal	May 2014
Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors Seifert, Roland; Wenzel-Seifert, Katharina Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 366, Issue 5 https://doi.org/10.1007/s00210-002-0588-0	journal	November 2002
electronic Ligand Builder and Optimization Workbench ( eLBOW ): a tool for ligand coordinate and restraint generation Moriarty, Nigel W.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 10 https://doi.org/10.1107/S0907444909029436	journal	September 2009
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy Zheng, Shawn Q.; Palovcak, Eugene; Armache, Jean-Paul Nature Methods, Vol. 14, Issue 4 https://doi.org/10.1038/nmeth.4193	journal	February 2017
Automation of the CHARMM General Force Field (CGenFF) II: Assignment of Bonded Parameters and Partial Atomic Charges Vanommeslaeghe, K.; Raman, E. Prabhu; MacKerell, A. D. Journal of Chemical Information and Modeling, Vol. 52, Issue 12 https://doi.org/10.1021/ci3003649	journal	November 2012
Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types Klauda, Jeffery B.; Venable, Richard M.; Freites, J. Alfredo The Journal of Physical Chemistry B, Vol. 114, Issue 23 https://doi.org/10.1021/jp101759q	journal	June 2010
CHARMM36m: an improved force field for folded and intrinsically disordered proteins Huang, Jing; Rauscher, Sarah; Nawrocki, Grzegorz Nature Methods, Vol. 14, Issue 1 https://doi.org/10.1038/nmeth.4067	journal	November 2016
Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning Hopkins, Chad W.; Le Grand, Scott; Walker, Ross C. Journal of Chemical Theory and Computation, Vol. 11, Issue 4 https://doi.org/10.1021/ct5010406	journal	March 2015
Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders Campos, Alline Cristina; Moreira, Fabricio Araújo; Gomes, Felipe Villela Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 367, Issue 1607 https://doi.org/10.1098/rstb.2011.0389	journal	December 2012
Crystal structures of agonist-bound human cannabinoid receptor CB1 Hua, Tian; Vemuri, Kiran; Nikas, Spyros P. Nature, Vol. 547, Issue 7664 https://doi.org/10.1038/nature23272	journal	July 2017
Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids Jorgensen, William L.; Maxwell, David S.; Tirado-Rives, Julian Journal of the American Chemical Society, Vol. 118, Issue 45 https://doi.org/10.1021/ja9621760	journal	January 1996
The Phenix software for automated determination of macromolecular structures Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Methods, Vol. 55, Issue 1 https://doi.org/10.1016/j.ymeth.2011.07.005	journal	September 2011
Identification of MDMB-FUBINACA in commercially available e-liquid formulations sold for use in electronic cigarettes Peace, Michelle R.; Krakowiak, Rose I.; Wolf, Carl E. Forensic Science International, Vol. 271 https://doi.org/10.1016/j.forsciint.2016.12.031	journal	February 2017
Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to Δ9-THC: Mechanism underlying greater toxicity? Fantegrossi, William E.; Moran, Jeffery H.; Radominska-Pandya, Anna Life Sciences, Vol. 97, Issue 1 https://doi.org/10.1016/j.lfs.2013.09.017	journal	February 2014
The Effect of pH on β2 Adrenoceptor Function Ghanouni, Pejman; Schambye, Hans; Seifert, Roland Journal of Biological Chemistry, Vol. 275, Issue 5 https://doi.org/10.1074/jbc.275.5.3121	journal	February 2000
Structural Mimicry in Class A G Protein-coupled Receptor Rotamer Toggle Switches McAllister, Sean D.; Hurst, Dow P.; Barnett-Norris, Judy Journal of Biological Chemistry, Vol. 279, Issue 46 https://doi.org/10.1074/jbc.M406648200	journal	November 2004
UCSF ChimeraX: Meeting modern challenges in visualization and analysis: UCSF ChimeraX Visualization System Goddard, Thomas D.; Huang, Conrad C.; Meng, Elaine C. Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3235	journal	September 2017
Cryo-EM structure of human rhodopsin bound to an inhibitory G protein Kang, Yanyong; Kuybeda, Oleg; de Waal, Parker W. Nature, Vol. 558, Issue 7711 https://doi.org/10.1038/s41586-018-0215-y	journal	June 2018
Molecular modeling of organic and biomolecular systems usingBOSS andMCPRO Jorgensen, William L.; Tirado-Rives, Julian Journal of Computational Chemistry, Vol. 26, Issue 16 https://doi.org/10.1002/jcc.20297	journal	January 2005
Agonist alkyl tail interaction with cannabinoid CB1 receptor V6.43/I6.46 groove induces a helix 6 active conformation Barnett-Norris, Judy; Hurst, Dow P.; Buehner, Kurt International Journal of Quantum Chemistry, Vol. 88, Issue 1 https://doi.org/10.1002/qua.10093	journal	January 2002
Pharmacological evaluation of new constituents of “Spice”: synthetic cannabinoids based on indole, indazole, benzimidazole and carbazole scaffolds Schoeder, Clara T.; Hess, Cornelius; Madea, Burkhard Forensic Toxicology, Vol. 36, Issue 2 https://doi.org/10.1007/s11419-018-0415-z	journal	April 2018
Accuracy of free energies of hydration using CM1 and CM3 atomic charges Udier-Blagovi?, Marina; Morales De Tirado, Patricia; Pearlman, Shoshannah A. Journal of Computational Chemistry, Vol. 25, Issue 11 https://doi.org/10.1002/jcc.20059	journal	January 2004
The Endocannabinoid System and Pain Guindon, Josee; Hohmann, Andrea CNS & Neurological Disorders - Drug Targets, Vol. 8, Issue 6 https://doi.org/10.2174/187152709789824660	journal	December 2009
New tools for the analysis and validation of cryo-EM maps and atomic models Afonine, Pavel V.; Klaholz, Bruno P.; Moriarty, Nigel W. Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 9 https://doi.org/10.1107/S2059798318009324	journal	September 2018
Structural basis for nucleotide exchange in heterotrimeric G proteins Dror, R. O.; Mildorf, T. J.; Hilger, D. Science, Vol. 348, Issue 6241 https://doi.org/10.1126/science.aaa5264	journal	June 2015
Crystal Structure of a Lipid G Protein-Coupled Receptor Hanson, M. A.; Roth, C. B.; Jo, E. Science, Vol. 335, Issue 6070 https://doi.org/10.1126/science.1215904	journal	February 2012
Concurrent Stimulation of Cannabinoid CB1 and Dopamine D2 Receptors Augments cAMP Accumulation in Striatal Neurons: Evidence for a G _s Linkage to the CB1 Receptor Glass, Michelle; Felder, Christian C. The Journal of Neuroscience, Vol. 17, Issue 14 https://doi.org/10.1523/JNEUROSCI.17-14-05327.1997	journal	July 1997
Automated electron microscope tomography using robust prediction of specimen movements Mastronarde, David N. Journal of Structural Biology, Vol. 152, Issue 1 https://doi.org/10.1016/j.jsb.2005.07.007	journal	October 2005
Structure and function of an irreversible agonist-β2 adrenoceptor complex Rosenbaum, Daniel M.; Zhang, Cheng; Lyons, Joseph A. Nature, Vol. 469, Issue 7329 https://doi.org/10.1038/nature09665	journal	January 2011

Cited By (25)

Cryo-EM structure of oxysterol-bound human Smoothened coupled to a heterotrimeric Gi Qi, Xiaofeng; Liu, Heng; Thompson, Bonne Nature, Vol. 571, Issue 7764 https://doi.org/10.1038/s41586-019-1286-0	journal	June 2019
Functional evaluation of carboxy metabolites of synthetic cannabinoid receptor agonists featuring scaffolds based on L‐valine or L‐ tert ‐leucine Wouters, Elise; Mogler, Lukas; Cannaert, Annelies Drug Testing and Analysis, Vol. 11, Issue 8 https://doi.org/10.1002/dta.2607	journal	May 2019
Structure of formylpeptide receptor 2-Gi complex reveals insights into ligand recognition and signaling Zhuang, Youwen; Liu, Heng; Edward Zhou, X. Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-14728-9	journal	February 2020
Differential activation of G protein‐mediated signaling by synthetic cannabinoid receptor agonists Sachdev, Shivani; Banister, Samuel D.; Santiago, Marina Pharmacology Research & Perspectives, Vol. 8, Issue 2 https://doi.org/10.1002/prp2.566	journal	February 2020
Modulation of Mast Cell Reactivity by Lipids: The Neglected Side of Allergic Diseases Hagemann, Philipp M.; Nsiah-Dosu, Stephanie; Hundt, Jennifer Elisabeth Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.01174	journal	May 2019
Molecular Pharmacology of Class F Receptor Activation Kozielewicz, Pawel; Turku, Ainoleena; Schulte, Gunnar Molecular Pharmacology, Vol. 97, Issue 2 https://doi.org/10.1124/mol.119.117986	journal	October 2019
Cryo-EM structure of the rhodopsin-Gαi-βγ complex reveals binding of the rhodopsin C-terminal tail to the gβ subunit Tsai, Ching-Ju; Marino, Jacopo; Adaixo, Ricardo eLife, Vol. 8 https://doi.org/10.7554/elife.46041	journal	June 2019
Cannabinoid Receptor Interacting Protein 1a (CRIP1a): Function and Structure Booth, William T.; Walker, Noah B.; Lowther, W. Todd Molecules, Vol. 24, Issue 20 https://doi.org/10.3390/molecules24203672	journal	October 2019
Impacts of cannabinoid epigenetics on human development: reflections on Murphy et. al. ‘cannabinoid exposure and altered DNA methylation in rat and human sperm’ epigenetics 2018; 13: 1208-1221. Reece, Albert Stuart; Hulse, Gary Kenneth Epigenetics, Vol. 14, Issue 11 https://doi.org/10.1080/15592294.2019.1633868	journal	June 2019
Cannabinoid Receptor Interacting Protein 1a (CRIP1a): Function and Structure Booth, William T.; Walker, Noah B.; Lowther, W. Todd Molecules, Vol. 24, Issue 20 https://doi.org/10.3390/molecules24203672	journal	October 2019
Enantiospecific Synthesis, Chiral Separation, and Biological Activity of Four Indazole-3-Carboxamide-Type Synthetic Cannabinoid Receptor Agonists and Their Detection in Seized Drug Samples Antonides, Lysbeth H.; Cannaert, Annelies; Norman, Caitlyn Frontiers in Chemistry, Vol. 7 https://doi.org/10.3389/fchem.2019.00321	journal	May 2019
Impacts of cannabinoid epigenetics on human development: reflections on Murphy et. al. ‘cannabinoid exposure and altered DNA methylation in rat and human sperm’ epigenetics 2018; 13: 1208-1221. Reece, Albert Stuart; Hulse, Gary Kenneth Epigenetics, Vol. 14, Issue 11 https://doi.org/10.1080/15592294.2019.1633868	journal	June 2019
Non-Functional Trace Amine-Associated Receptor 1 Variants in Patients With Mental Disorders Rutigliano, Grazia; Bräunig, Julia; Del Grande, Claudia Frontiers in Pharmacology, Vol. 10 https://doi.org/10.3389/fphar.2019.01027	journal	September 2019
Systematic Affinity Purification Coupled to Mass Spectrometry Identified p62 as Part of the Cannabinoid Receptor CB2 Interactome Sharaf, Ahmed; Mensching, Leonore; Keller, Christina Frontiers in Molecular Neuroscience, Vol. 12 https://doi.org/10.3389/fnmol.2019.00224	journal	September 2019
Detection and quantitation of synthetic cannabinoid receptor agonists in infused papers from prisons in a constantly evolving illicit market Norman, Caitlyn; Walker, Gillian; McKirdy, Brian Drug Testing and Analysis, Vol. 12, Issue 4 https://doi.org/10.1002/dta.2767	journal	April 2020
Non-Functional Trace Amine-Associated Receptor 1 Variants in Patients With Mental Disorders Rutigliano, Grazia; Bräunig, Julia; Del Grande, Claudia Frontiers in Pharmacology, Vol. 10 https://doi.org/10.3389/fphar.2019.01027	journal	September 2019
Allosteric Modulation of Cannabinoid Receptor 1—Current Challenges and Future Opportunities International Journal of Molecular Sciences, Vol. 20, Issue 23 https://doi.org/10.3390/ijms20235874	journal	November 2019
The chemistry and pharmacology of putative synthetic cannabinoid receptor agonist (SCRA) new psychoactive substances (NPS) 5F‐PY‐PICA, 5F‐PY‐PINACA, and their analogs Banister, Samuel D.; Kevin, Richard C.; Martin, Lewis Drug Testing and Analysis, Vol. 11, Issue 7 https://doi.org/10.1002/dta.2583	journal	March 2019
Conformational plasticity of the intracellular cavity of GPCR−G-protein complexes leads to G-protein promiscuity and selectivity Sandhu, Manbir; Touma, Anja M.; Dysthe, Matthew Proceedings of the National Academy of Sciences https://doi.org/10.1073/pnas.1820944116	journal	May 2019
Cryo-EM structure of the rhodopsin-Gαi-βγ complex reveals binding of the rhodopsin C-terminal tail to the gβ subunit Tsai, Ching-Ju; Marino, Jacopo; Adaixo, Ricardo ETH Zurich https://doi.org/10.3929/ethz-b-000355900	text	January 2019
In vitro determination of the efficacy of illicit synthetic cannabinoids at CB ₁ receptors Sachdev, Shivani; Vemuri, Kiran; Banister, Samuel D. British Journal of Pharmacology, Vol. 176, Issue 24 https://doi.org/10.1111/bph.14829	journal	December 2019
Structure of formylpeptide receptor 2-Gi complex reveals insights into ligand recognition and signaling Zhuang, Youwen; Liu, Heng; Edward Zhou, X. Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-14728-9	journal	February 2020
Structure of an allosteric modulator bound to the CB1 cannabinoid receptor Shao, Zhenhua; Yan, Wei; Chapman, Karen Nature Chemical Biology, Vol. 15, Issue 12 https://doi.org/10.1038/s41589-019-0387-2	journal	October 2019
Control of glutamate release by complexes of adenosine and cannabinoid receptors Köfalvi, Attila; Moreno, Estefanía; Cordomí, Arnau BMC Biology, Vol. 18, Issue 1 https://doi.org/10.1186/s12915-020-0739-0	journal	January 2020
Adding more “spice” to the pot: A review of the chemistry and pharmacology of newly emerging heterocyclic synthetic cannabinoid receptor agonists Alam, Ryan M.; Keating, John J. Drug Testing and Analysis, Vol. 12, Issue 3 https://doi.org/10.1002/dta.2752	journal	January 2020

Similar Records

Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors

Journal Article · 2013 · Toxicology and Applied Pharmacology · OSTI ID:22285301

Rajasekaran, Maheswari; Brents, Lisa K.; Franks, Lirit N.; +1 more

Crystal structure of the β₂ adrenergic receptor-Gs protein complex

Journal Article · 2011 · Nature · OSTI ID:1026537

Rasmussen, Søren G.F.; DeVree, Brian T; Zou, Yaozhong; +17 more

CB1 and CB2 receptors are novel molecular targets for Tamoxifen and 4OH-Tamoxifen

Journal Article · 2013 · Biochemical and Biophysical Research Communications · OSTI ID:22242189

Prather, Paul L.; FrancisDevaraj, FeAna; Dates, Centdrika R.; +5 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
cannabinoid receptor
CB1
GPCR
cryo-EM
synthetic cannabinoid
Fubinaca
Gi

Title: Structure of a Signaling Cannabinoid Receptor 1-G Protein Complex

Citation Formats

References (78)

Cited By (25)

Similar Records

Related Subjects