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December 2021 "Meet Peter McNamara, Ph.D., Tectonic’s SVP, Head of Research. Peter joined Tectonic to help chart new territory in GPCR science. We’re glad to have Peter's dedication, experience, and passion in building innovative therapeutics."

Peter Banks, Scientific Director at BioTek Instruments! Learn about his career today!

Thomas P.

Next on the Dr. GPCR Podcast, we have Dr. Nicola Smith, Molecular Pharmacologist, lab head, and senior lecturer at UNSW Sydney. Subscribe to the podcast today and get notified when new episodes are released! Please share! https://www.ecosystem.drgpcr.com/dr-gpcr-podcast/ #gpcr #drgpcr #podcast

March 2022 "Congratulations to Richard J. Law, our newly named Chief Business Officer.

November 2021 "So proud and grateful to receive honorary doctorate yesterday from Karolinska Institute and celebrate with my family in Stockholm." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) lipids have been shown to stabilize an active conformation of class A G-protein coupled receptors (GPCRs) through a conserved binding site, not present in class B GPCRs. For class B GPCRs, previous molecular dynamics (MD) simulation studies have shown PI(4,5)P2 interacting with the Glucagon receptor (GCGR), which constitutes an important target for diabetes and obesity therapeutics. In this work, we applied MD simulations supported by native mass spectrometry (nMS) to study lipid interactions with GCGR. We demonstrate how tail composition plays a role in modulating the binding of PI(4,5)P2 lipids to GCGR. Specifically, we find the PI(4,5)P2 lipids to have a higher affinity toward the inactive conformation of GCGR. Interestingly, we find that in contrast to class A GPCRs, PI(4,5)P2 appear to stabilize the inactive conformation of GCGR through a binding site conserved across class B GPCRs but absent in class A GPCRs. This suggests differences in the regulatory function of PI(4,5)P2 between class A and class B GPCRs." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 "In the Wnt-β-catenin pathway, Wnt binding to Frizzled (Fzd) and LRP5 or LRP6 (LRP5/6) co-receptors inhibits the degradation of the transcriptional coactivator β-catenin by recruiting the cytosolic effector Dishevelled (Dvl). Polymerization of Dvl at the plasma membrane recruits the β-catenin destruction complex, enabling the phosphorylation of LRP5/6, a key step in inhibiting β-catenin degradation. Using purified Fzd proteins reconstituted in lipid nanodiscs, we investigated the factors that promote the recruitment of Dvl to the plasma membrane. We found that the affinity of Fzd for Dvl was not affected by Wnt ligands, in contrast to other members of the GPCR superfamily for which the binding of extracellular ligands affects the affinity for downstream transducers. Instead, Fzd-Dvl binding was enhanced by increased concentration of the lipid PI(4,5)P2, which is generated by Dvl-associated lipid kinases in response to Wnt and which is required for LRP5/6 phosphorylation. Moreover, binding to Fzd did not promote Dvl DEP domain dimerization, which has been proposed to be required for signaling downstream of Fzd. Our findings suggest a positive feedback loop in which Wnt-stimulated local PI(4,5)P2 production enhances Dvl recruitment and further PI(4,5)P2 production to support Dvl polymerization, LRP5/6 phosphorylation, and β-catenin stabilization." Read more at the source #DrGPCR #GPCR #IndustryNews

and antihistamines: A clinical trial is needed Jillian G Baker ,  Erica K Sloan ,   Kevin Pfleger ,  Peter receptors, data mapper, structure similarity search and models of physiological ligand complexes Luis P Taracena Herrera , Søren N Andreassen ,   Jimmy Caroli ,   Albert J Kooistra , Gáspár Pándy-Szekeres at two distinct sites of a human bitter taste GPCR Lior Peri ,  Donna Matzov ,  Dominic R Huxley ,   Peter Gmeiner ,  Peter J McCormick ,  Dorothee Weikert ,  Masha Y Niv ,  Moran Shalev-Benami , et al.

J., Fung, J. J., Pardon, E., Casarosa, P., Chae, P. S., Devree, B. T., Rosenbaum, D. M., Thian, F. M., Manglik, A., Hu, J., Hu, K., Eitel, K., Hübner, H., Pardon, E., Valant, C., Sexton, P. C., Gmeiner, P., Steyaert, J., Weis, W. I., Garcia, K. C., Wess, J., & Kobilka, B. K. (2013). Nature, 504(7478), 101–106. https://doi.org/10.1038/nature12735 Burg, J. S., Ingram, J. D., Tworak, A., Watanabe, K., Pardon, E., Steyaert, J., Kandori, H., Katayama, K., Kiser, P.

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phosphorylation of the G protein subunit Gαi at specific residues within three strategic hotspots: the P Key findings include: Phosphorylation Hotspots: P Loop (Ser44, Ser47, Thr48): Impairs ligand-stimulated Signaling Pathway Segregation: Phosphorylation events in the interdomain cleft and P loop uncouple G J., Ghassemian, M., Kufareva, I., & Ghosh, P. (2024).

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in-depth-molecular-profiling-of-an-intronic-gnao1-mutant-as-the-basis-for-personalized-high-throughput-drug-screening References Grimes, J. M., Medel-Lacruz, B., Baidya, M., Makarova, M., Mistry, R., Goulding, J., Drube, J., Hoffmann, C., Owen K., Selent, J., Hill, S. J., & Calebiro, D. (2023). Cell, 186(10), 2238–2255.e20. https://doi.org/10.1016/j.cell.2023.04.018 Janetzko, J., Kise, R., Barsi-Rhyne Toxicol. 52, 179–197. https://doi.org/10. 1146/annurev.pharmtox.010909.105800 Tsao, P.

., Stephany, J. J., & Fields, S. (2014). -P., Macdonald, C. B., Mehrotra, E., Patrick Rockefeller Grimes, Zahm, A. M., Trinidad, D. ., English, J. G., Coyote-Maestas, W., & Aashish Manglik. (2024).

Embo j, 2012. 31(6): p. 1364-78. 2. Xiao, P., et al., Tethered peptide activation mechanism of the adhesion GPCRs ADGRG2 and ADGRG4. Nature, 2022. 604(7907): p. 628-630. 7. ., Liang, J., Duan, Y., Yin, H., Xiong, Y., Zhang, A., Guo, C., Chen, Z., Huang, Z., & He, Y. (2022).

Robert J Lefkowitz and team's study 'GPCR signal transduction: β-arrestin activates ERK MAPK.' Dr. Thomas P. J. Silvio Gutkind.

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Expression "P-glycoprotein (P-gp) is a key component of the intestinal epithelium playing a pivotal secondary bile acids, produced by the intestinal microbiome, potentiate the induction of functional P-gp We now aim to determine the molecular mechanism by which this functional microbiome output regulates P-gp combination discovered a unique transcriptional program involving multiple pathways that converge on P-gp on a sophisticated signaling network directed by intestinal microbial metabolites that orchestrate P-gp

clinical parameters such as alpha-fetoprotein and tumor grade in the HCC patients; (c) besides HCC (p was found to be an important factor for survival in four other cancers (clear renal cell carcinoma: p < 0.001, lung adenocarcinoma: p = 0.004, mesothelioma: p = 0.039, ovarian serous cystadenocarcinoma: p = 0.048); (d) RGS20 was found to be significantly associated with some tumor-related signaling pathways

References: Lyu, J. et al. AlphaFold2 structures guide prospective ligand discovery. Science https://doi.org/10.1126/science.adn6354 (2024) Abramson, J., Adler, J., Dunger, J. et al.

Bryan Roth, Peter Gmeiner, and Thomas P. Sakmar this week. For Dr.

of patients showed high GPER expression and significant correlation with the mRNA subtype of TNBC (P  = 0.001), total metastatic events (P = 0.019) and liver metastasis (P = 0.011). interval of 67.1 months, a significant trend towards reduced distant metastasis-free survival (DMFS) (P 

2016) where O-glycosylation contributes to the differential binding to CC or CX3C chemokine (Casarosa P sites in their N-termini that mediate ligand binding and signaling (Bannert N et al. 2001; Casarosa P et al. 2005; Gao J et al. 2003; Fieger CB et al. 2005). glycosulfo peptide analogue GSnP-6 displays nanomolar affinity and promising potential for blocking PSGL-1/P-selectin