An analysis of mutual interactions of subunits in the C5aR1-G protein complex has provided new insights

Sexton et al. for their job on Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP Please complete this form to take advantage of this opportunity. It doesn’t have to be a complete poster, just a few slides to spark the conversation. If you've participated in our symposiums, please take a few minutes to complete this survey. protein coupling specificity at a class A GPCR Cryo-EM Structure of the Human Amylin 1 Receptor in Complex

Kathleen M Caron and her team studied the GPER/GPR30 complex with β1-adrenergic receptor and AKAP5 in GPCR University February 8 - 29: Join Dr. GPCR University's live course with Dr. Terry Kenakin. Kenakin and your classmates Access to the course materials and recordings Course completion certificate auditory neurons GPCRs in Oncology and Immunology G protein-coupled estrogen receptor (GPER)/GPR30 forms a complex

Hello GPCR people! Check out our GPCR roundup now, and be the first to read! This week's highlight: Congrats to our partner GPCR Therapeutics, on their expansion into fibrosis with their new research. Save the dates: November 2 - 4: We're sponsoring the GPCR Retreat and would love to meet you there! Join the waitlist by emailing gpcrretreat@uottawa.ca. Submit a logo design by Nov 1st on the Logo Contest page. No registration is needed to submit your logo design. Subscribe now to Dr. GPCR Newsletter to get more info! Check out the weekly Classified GPCR News from October 2nd to 8th, 2023. GPCR Binders, Drugs, and more In silico identification of a biarylamine acting as agonist at human β3 adrenoceptors and exerting BRL37344-like effects on mouse metabolism Development, synthesis and evaluation of novel fluorescent Endothelin-B receptor probes GPCRs in Cardiology, Endocrinology, and Taste GPRASP1 loss-of-function links to arteriovenous malformations by endothelial activating GPR4 signals GPCRs in Neuroscience Involvement of a silkworm D2-like dopamine receptor in the promotion of feeding and related behaviors Methods & Updates in GPCR Research Functional GPCR expression in eukaryotic LEXSY system Structural and Molecular Insights into GPCR Function Interplay of Cholesterol and Actin in Neurotransmitter GPCR Signaling: Insights from Chronic Cholesterol Depletion Using Statin Side-Chain Dynamics of the α1B -Adrenergic Receptor determined by NMR via Methyl Relaxation Structural determinants of sphingosine-1-phosphate receptor selectivity Industry News Sosei Heptares and Verily Nominate First G-protein-coupled receptor Target for Therapeutic Development DKK 25 million to development of databases supporting medical research ‘Define your own success’: Duke leaders talk success, failure at symposium honoring Nobel Laureate Robert Lefkowitz Integral Molecular Secures Nearly $900K in NIH Funding to Discover Antibodies Against Difficult and Conserved Protein Targets GPCR Therapeutics Expands Pipeline into Fibrosis with a Combination Approach Targeting LPA1 GPCR Events, Meetings, and Webinars October 25 - 27, 2023 | 3rd Annual Meeting IRN I-GPCRNet November 2 - 4, 2023 | GPCR Retreat- Registration Closed November 15 - 17, 2023 | MPGPCR Conference November 20 - 23, 2023 | ASCEPT Annual Scientific Meeting February 3 - 7, 2024 | SLAS2024 International Conference and Exhibition March 23 - 24, 2024 | Ligand Recognition and Molecular Gating Seminar March 24 - 29, 2024 | Ligand Recognition and Molecular Gating Conference April 5 - 10, 2024 | AACR Annual Meeting May 13 - 17, 2024 | 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference and Exhibition June 2 - 4, 2024 | Chemotactic Cytokines GPCR Jobs NEW Senior Scientist, In vitro pharmacology - Crinetics Pharmaceuticals NEW Senior Director, In vitro pharmacology - Crinetics Pharmaceuticals In vivo Antibody Discovery Research Scientist In Vitro Biologist/Molecular Pharmacologist Senior Vice President, Oncology Clinical Research Scientist (level I or II) Research Fellow Research Technician II - Surgery Post-Doc Research Associate Research Technician Explore Dr. GPCR Ecosystem

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Hello Readers👋, We're excited to share our weekly newsletter with you. Keep up-to-date with the latest research and advancements in the field with our convenient, weekly news delivered to your inbox. You can always adjust your email preferences in your account settings. Below is your Classified GPCR News at a glance for January 2nd to January 8th, 2023. GPCR Activation and Signaling Signal Transduction and Gene Regulation in the Endothelium. Pharmacological Profiling of a Brugia malayi Muscarinic Acetylcholine Receptor as a Putative Antiparasitic Target. GPCR Signaling Measurement and Drug Profiling with an Automated Live-Cell Microscopy System. GPCR Binders, Drugs, and more Cytotoxicity-related effects of imidazolium and chlorinated bispyridinium oximes in SH-SY5Y cells. GPCRs in Neuroscience Filamin A organizes γ‑aminobutyric acid type B receptors at the plasma membrane. GPCRs in Oncology and Immunology Vasoactive intestinal peptide receptor 2 signaling promotes breast cancer cell proliferation by enhancing the ERK pathway. Methods & Updates in GPCR Research Small Molecule Tools to Study Cellular Target Engagement for the Intracellular Allosteric Binding Site of GPCRs. Structural and Molecular Insights into GPCR Function Structural and functional analyses of a GPCR-inhibited ion channel TRPM3. Industry News Arcoscreen selected by START Lausanne to pitch at the START Global summit on the 23-24th March 2023. Twist Bioscience and Astellas Enter into Multitarget Antibody Discovery Research Collaboration Neurocrine Biosciences and Voyager Therapeutics Enter Strategic Collaboration for Development and Commercialization of Voyager’s GBA1 Program and Other Next-Generation Gene Therapies for Neurological Diseases Crinetics Pharmaceuticals To Present Corporate And Clinical Update At 41st Annual J.P. Morgan Healthcare Conference Neurocrine Biosciences, Inc.'s Director Stephen A. Sherwin Sells 30,000 Shares STALICLA signs agreement with Novartis on neurodevelopmental disorders Call for GPCR Papers GPCRs: Signal Transduction. Deadline February 12, 2023 Current Technologies To Understand G-Protein-Coupled Receptor Molecular Pharmacology. Deadline January 30, 2023. GPCR Events, Meetings, and Webinars 2nd GPCR-Targeted Drug Discovery Summit | February 21-23, Boston. 2nd ERNEST Training School – February 20th to March 3rd. GEM2023 (14-17 March 2023). 8th and final ERNEST Meeting May 3-7, 2023 in Crete. The Illuminating the Understudied Druggable Proteome Conference. June 4-8,2023. 2023 Molecular Pharmacology (GRS) Seminar GRC. June 10 - 11. Progressive Technologies and Approaches Revealing Novel GPCR Biology and Drug Development Potential. June 11-16, 2023. 19th World Congress of Basic & Clinical Pharmacology 2023. July 2 - 7. GPCR Jobs Biotechnology and Biological Sciences Doctoral Training Programme Senior QM Manager Director of Molecular Pharmacology, Discovery Biology Staff Scientist/Senior Staff Scientist, Disease Biology and Translational Sciences Senior Scientist, Drug Metabolism and Pharmacokinetics PhD Opportunity - Investigation Of The Role Of The Formyl Peptide Receptor 2 In Diabetic Retinopathy PhD Opportunity - Novel P2y Receptor Ligands For Drug Discovery Explore Dr. GPCR Ecosystem

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structure of the Fgr SH3 domain at 1.9 Å resolution and developed a model for the GPCR-arrestin-3-Fgr complex

cryo-electron microscopy active structure of the wild-type arginine-vasopressin V2 receptor (V2R) in complex Overall, these findings highlight a notable structural variability among GPCR-arrestin signaling complexes

agonists with very slow off-rates can cause the formation of particularly stable receptor-arrestin complexes

We report the cryo-EM structures of β1-adrenergic receptor (β1-AR) in complex with Gs (GαsGβ1Gγ2) and a partial agonist or a very weak partial agonist, and compare them to the β1-AR-Gs structure in complex Analyses reveal similar overall complex architecture, with local conformational differences. Biochemical investigations uncover that the intermediate state complex comprising β1-AR and nucleotide-free simulations support the local conformational flexibilities and different stabilities among the three complexes

September 2022 Fly casting with ligand sliding and orientational selection supporting complex formation The deepest basin in the resultant free-energy landscape was assigned to native-like complex conformation Eventually, the native-like complex is completed.

which is in accordance with our findings demonstrating the prevalence of 5-HT2A–TrkB heteroreceptor complexes

GPCRs Are Optimal Regulators of Complex Biological Systems and Orchestrate the Interface between Health signaling systems is likely to be closely associated with disease-associated changes in organismal tissue complexity The ability of these receptorsomes (often in the absence of typical cell surface ligands) to control complex

August 2022 "Aims: The pathophysiological mechanism(s) underlying non-alcoholic fatty liver disease (NAFLD) have yet to be fully delineated and only a single drug, peroxisome proliferator-activated receptor (PPAR) α/γ agonist saroglitazar, has been approved. Here, we sought to investigate the role of Regulator of G Protein Signaling 7 (RGS7) in hyperlipidemia-dependent hepatic dysfunction. " Read more at the source #DrGPCR #GPCR #IndustryNews

Self-docking and cross-docking simulations of G protein-coupled receptor-ligand complexes: Impact of allow critical analysis of the potential interactions between small molecules and proteins in resulting complexes

October 2022 "The role of different G protein-coupled receptors (GPCRs) in the cardiovascular system is well understood in cardiomyocytes and vascular smooth muscle cells (VSMCs). In the former, stimulation of Gs-coupled receptors leads to increases in contractility, whereas stimulation of Gq-coupled receptors modulates cellular survival and hypertrophic responses. In VSMCs, stimulation of GPCRs also modulates contractile and cell growth phenotypes. Here, we will focus on the relatively less well-studied effects of GPCRs in cardiac fibroblasts, focusing on key signaling events involved in the activation and differentiation of these cells. We also review the hierarchy of signaling events driving the fibrotic response and the communications between fibroblasts and other cells in the heart. We discuss how such events may be distinct depending on where the GPCRs and their associated signaling machinery are localized in these cells with an emphasis on nuclear membrane-localized receptors. Finally, we explore what such connections between the cell surface and nuclear GPCR signaling might mean for cardiac fibrosis." Read more at the source #DrGPCR #GPCR #IndustryNews

Surprisingly, phosphorylation of the RGS promotes completion of cytokinesis before pheromone-induced Completion of cytokinesis in the presence of pheromone is promoted by the kelch-repeat protein, Kel1 We found that RGS complexes with Kel1 and prefers the unphosphorylatable RGS mutant. These data lead us to a model where Kel1 promotes completion of cytokinesis before pheromone-induced

August 2022 GPCRs steer G i and G s selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors "Serotonin (or 5-hydroxytryptamine, 5-HT) is an important neurotransmitter that activates 12 different G protein-coupled receptors (GPCRs) through selective coupling of Gs, Gi, or Gq proteins. The structural basis for G protein subtype selectivity by these GPCRs remains elusive. Here, we report the structures of the serotonin receptors 5-HT4, 5-HT6, and 5-HT7 with Gs, and 5-HT4 with Gi1. The structures reveal that transmembrane helices TM5 and TM6 alternate lengths as a macro-switch to determine receptor's selectivity for Gs and Gi, respectively. We find that the macro-switch by the TM5-TM6 length is shared by class A GPCR-G protein structures. Furthermore, we discover specific residues within TM5 and TM6 that function as micro-switches to form specific interactions with Gs or Gi. Together, these results present a common mechanism of Gs versus Gi protein coupling selectivity or promiscuity by class A GPCRs and extend the basis of ligand recognition at serotonin receptors." Read more at the source #DrGPCR #GPCR #IndustryNews

April 2022 Addex Therapeutics Completes Patient Enrollment For Dipraglurant Blepharospasm Phase 2 Clinical allosteric modulation-based drug discovery and development, announced today that patient enrollment has been completed

January 2022 Inversago Pharma Completes Phase 1 Clinical Trial on First-in-Class, Peripheral CB1 Blocker and Provides Strategy Update "Company has completed the Phase 1 Clinical Trial for its INV-202 molecule (“Inversago”), the peripheral CB1 blockade company, announced today the successful completion of the Phase 1 Clinical Trial for its INV-202 molecule that focuses on treating metabolic disorder complications

crystallize flexible membrane proteins, transient multiprotein assemblies, and individual molecules of complex conformations of proteins, including unstable structural intermediates and substates of conformationally complex Nb35: This nanobody selectively binds to the β2AR·Gs complex and prevents the dissociation of the nucleotide-free complex by the nonhydrolyzable GTP analog GTPγS4. Nb37: Similar to Nb35, this nanobody selectively binds to the β2AR·Gs complex and helps reveal the conformational

conformational changes that allow the coupling and subsequent activation of the G-protein heterotrimeric complex Besides the differences in their structural complexity, some members of the RGS family are selective these proteins has been implicated in a range of diseases, and understanding the mechanisms of these complex Zhuang, Y., et al., Structural insights into the human D1 and D2 dopamine receptor signaling complexes J Neurosci, 2019. 39(42): p. 8291-8304. https://pubmed.ncbi.nlm.nih.gov/31308097/ 8.

Save the date: February 8 - 29: Join Dr. GPCR University's live Zoom sessions hosted by Dr. Kenakin and your classmates Access to the course materials and recordings once the course is completed Course completion certificate signed by Dr. Spatiotemporal Optical Control of Gαq-PLCβ Interactions Snapshot of the cannabinoid receptor 1-arrestin complex AlphaFold and Experimental Structures for the Prediction of the Structure and Binding Affinities of GPCR Complexes

protein recruitment assay [6], mini-G recruitment assay [7], GRK and β-arrestin recruitment assays [8] advance, leveraging RET-based sensors will undoubtedly continue to propel our quest to unravel the complexities J Biol Chem, 2018. 293(19): p. 7466-7473. 8.      Nat Chem Biol, 2020. 16(8): p. 841-849. 10.   

GLP-1R [7], while GLP-1R is also known to heterodimerize with the GIPR in recombinant cell system [8] Perreault, M.L., et al., Heteromeric dopamine receptor signaling complexes: emerging neurobiology and Proc Natl Acad Sci U S A, 2012. 109 (45): p. 18607-12. 8.         

Early-bird registration and abstract submissions close on September 8, and final registration ends on nucleus accumbens Understanding the Molecular Regulation of Serotonin Receptor 5-HTR1B-β-Arrestin1 Complex Final Symposium (August 31 - September 1, 2023) 3rd Transatlantic ECI GPCR Symposium (September 7 - 8,

couple to G protein-coupled receptor kinases (GRKs) and recruit β-arrestins, adding another layer of complexity for cAMP production at the GLP-1R which minimal ability to recruit β-arrestins, relative to GLP-1 [8- Endocr Rev, 2023. 44 (3): p. 492-517. 8.