Extensive efforts of structural biology have been made on the study of GPCRs. However, a large portion of GPCR structures remain unsolved due to structural instability. Herein we evaluated the accuracy of GPCR structure models predicted by AlphaFold2. These differences impeded the use of predicted structure models in the functional study and structure-based drug design of GPCRs, which required reliable high-resolution structural information."

August 2022 Structure Therapeutics Extends Financing, Advances Diabetes and Obesity Clinical Program and Changes Name from ShouTi " San Francisco and Shanghai – August 1, 2022 – Structure Therapeutics (Structure Therapeutics), formerly known as ShouTi Inc., today announced it closed an oversubscribed In addition, Structure Therapeutics has completed dosing in a single ascending dose (SAD) Phase 1 study

October 2022 Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric Thus, we need to know much more about the structures of receptor-ligand complexes at high resolution. Constituent structural motifs cooperatively transform ligand selectivity into specific functions, thus conceptualizing the primacy of the 3D structure over individual motifs of receptors. This review covers the new data elucidating the structural dynamics of AngII receptors and how structural

Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights

In this article, we describe a 2.2 Å resolution room temperature crystal structure of the human S1P5 The structure demonstrates a unique ligand-binding mode, involving an allosteric sub-pocket, which clarifies the receptor subtype selectivity and provides a template for structure-based drug design. Together with previously published S1PR structures in complex with antagonists and agonists, our structure with S1P5-inverse agonist sheds light on the activation mechanism and reveals structural determinants

Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights

Structurally, the extensive extracellular domain, which contains the hormone-binding site and is linked

The structural basis for GPCR activation of down-stream signaling and regulatory proteins; and 4.

November 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed molecules) compounds were docked to an allosteric binding site of mGlu5 identified in X-ray crystal structures lead-like chemical libraries have complementary advantages and illustrate how access to high-resolution structures

October 2022 "Recently determined structures of class C G protein-coupled receptors (GPCRs) revealed molecules) compounds were docked to an allosteric binding site of mGlu5 identified in X-ray crystal structures lead-like chemical libraries have complementary advantages and illustrate how access to high-resolution structures

Our analysis suggests that the structures of GPCRs bound to these interaction partners available today orientation of individual residues and/or their interactions not easily detectable in the receptor-transducer structures partner preference; or (iii) the dynamics of GPCR binding to different types of partners rather than the structures

with definite sites and domains within SMO and relate them with known cholesterol-binding sequence and structure Structural analysis of SMO domains shows significant changes in the CRD and ICD, during the course of

HDX-MS-optimized approach to characterize nanobodies as tools for biochemical and structural studies single-chain camelid nanobodies using hydrogen-deuterium exchange (HDX) mass spectrometry (MS) for structural

Here, we discuss recent crystal structures of inactive C5aR1 in terms of an inverted orientation of helix H8, unobserved in other GPCR structures.

Recurrent high-impact mutations at cognate structural positions in class A G protein-coupled receptors They have a common structure and, signaling through a much smaller set of G proteins, arrestins, and

The experimental structure of these receptors has yet to be determined, and key-residues controlling

Sandra Berndt talk about new structural perspectives in GPCR-mediated Src family kinase activation.

August 2022 "Histamine exerts its physiological functions through its four receptor subtypes. In this work, we report the subcellular localization of histamine receptor 2 (H2R), a G protein-coupled receptor (GPCR), which is expressed in a wide variety of cell and tissue types. A growing number of GPCRs have been shown to be localized in the nucleus and contribute toward transcriptional regulation. In this study, for the first time, we demonstrate the nuclear localization of H2R in lymphatic endothelial cells. In the presence of its ligand, we show significant upregulation of H2R nuclear translocation kinetics. Using fluorescently tagged histamine, we explored H2R-histamine binding interaction, which exhibits a critical role in this translocation event. Altogether, our results highlight the previously unrecognized nuclear localization pattern of H2R. At the same time, H2R as a GPCR imparts many unresolved questions, such as the functional relevance of this localization, and whether H2R can contribute directly to transcriptional regulation and can affect lymphatic specific gene expression. H2R blockers are commonly used medications that recently have shown significant side effects. Therefore, it is imperative to understand the precise molecular mechanism of H2R biology. In this aspect, our present data shed new light on the unexplored H2R signaling mechanisms. This article has an associated First Person interview with the first author of the paper." Read more at the source #DrGPCR #GPCR #IndustryNews

bioinformatics tools showed that functional mutations in the ADGLR3 gene disrupt the standard and wild ADGRL3 structure

We hypothesized that there is a common set of receptor interactions made by ligands of diverse structures We computationally docked ~2700 known β2AR ligands to multiple β2AR structures, generating ca 75 000 interpretation of ML analysis in human understandable form allowed us to construct an exquisitely detailed structure‐activity

Papasergi-Scott, Peter Gmeiner, Brian K Kobilka, Georgios Skiniotis, et al. for their research on Time-resolved cryo-EM We're gearing up for our next symposium on June 7th, focusing on Structural and Molecular Insights into and quantify the COPII concentration and anterograde transport of nascent G protein-coupled receptors Structural and Molecular Insights into GPCR Function Time-resolved cryo-EM of G-protein activation by a GPCR Industry Prediction of Large, Complex Protein Structures Newly discovered adhesion GPCR mayo controls midgut

August 2022 "G-protein-coupled receptors (GPCR) are present at the cell surface in different conformational and oligomeric states. However, how these states impact GPCRs biological function and therapeutic targeting remains incompletely known. Here, we investigated this issue in living cells for the CC chemokine receptor 5 (CCR5), a major receptor in inflammation and the principal entry co-receptor for Human Immunodeficiency Viruses type 1 (HIV-1). We used TIRF microscopy and a statistical method to track and classify the motion of different receptor subpopulations. We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric states and exhibiting transient Brownian and restricted motions. These forms were stabilized differently by distinct ligands. In particular, agonist stimulation restricted the mobility of CCR5 and led to its clustering, a feature depending on β-arrestin, while inverse agonist stimulation exhibited the opposite effect. These results suggest a link between receptor activation and immobilization. Applied to HIV-1 envelope glycoproteins gp120, our quantitative analysis revealed agonist-like properties of gp120s. " Read more at the source #DrGPCR #GPCR #IndustryNews

We discuss ligand binding, signaling, and structures of the vGPCRs in light of robust differences from

To better understand the structural basis for this bias, we examined structural models of GPR35 and conducted

April is the month of DNA Day, a special day commemorating the discovery of the DNA double helix structure Advances in structural genomics, coupled with techniques like X-ray crystallography and cryo-electron microscopy, have allowed us to understand the structural dynamics during receptor activation. Structural bioinformatics analysis of variants on GPCR function. Time-resolved cryo-EM of G protein activation by a GPCR. bioRxiv : the preprint server for biology, 2023.03.20.533387

into the Classified GPCR News from February 26th to March 3rd, 2024 Adhesion GPCRs The repertoire and structure variants assembled from publicly available deep-sequenced human samples GPCR Activation and Signaling Structure-guided suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells Methods & Updates in GPCR Research Cryo-electron Commentary: Analyzing invertebrate bitopic cadherin G protein-coupled receptors that bind cry toxins antagonists for hyperthyroidism Unlocking the Secrets of Cellular Communication: The Revolutionary Impact of Cryo-EM

October 2022 "We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule fluorescence (SMF) spectroscopy. We explain in detail steps shared between the two sample preparation strategies, including expression and isolation of A2AAR and assembly of A2AAR in lipid nanodiscs and procedures for incorporation of either 19F-NMR or fluorescence probes. Protocols for SMF experiments include sample setup, data acquisition, data processing, and error analysis. For complete details on the use and execution of this protocol, please refer to Wei et al. (2022) and Sušac et al. (2018)." Read more at the source #DrGPCR #GPCR #IndustryNews

Our next symposium on Structural and Molecular Insights into GPCR Function. Updates in GPCR Research A multicolor suite for deciphering population coding of calcium and cAMP in vivo Cryo-EM advances in GPCR structure determination Visualization of endogenous G proteins on endosomes and other and human genetic disease Advances and challenges in cancer immunoprevention and immune interception Structural and Molecular Insights into GPCR Function Structural bioinformatics studies of serotonin, dopamine and