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.- Jan Steyaert, scientific director of the VIB-VUB Center for Structural Biology, Vlaams Instituut Biotechnologie the mechanistic understanding of one of the biggest classes of pharmaceutical targets by combining structural biology and advanced biotechnology."

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."

VIB spin-off Confo Therapeutics today announced that it has entered into a collaborative agreement with

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

Recent structural studies shed light on the molecular mechanisms involved in GPCR-arrestin coupling, Here, we report the cryo-electron microscopy active structure of the wild-type arginine-vasopressin V2 terminus are clearly identified and interact extensively with the β-arrestin1 N-lobe, in agreement with structural Overall, these findings highlight a notable structural variability among GPCR-arrestin signaling complexes

The recently determined structures of B2R have provided molecular insights into the functions and regulation of B2R, which shed light on structure-based drug design for the treatment of B2R-related diseases. In this review, we summarize the structure and function of B2R in relation to drug discovery and discuss

Currently, there are more than 40 available structures of chemokines and their receptors in the Protein Data Bank (PDB) which reveal common structural features, such as the presence of seven transmembrane A recent comparative analysis study of all structures of CKRs characterizes the molecular recognition Chemokine Binding Mode – from CRS1 to CRS3 Chemokines possess a conserved tertiary structure known as These two sites are observed in all typical CKR-chemokine structures.

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 Inc (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

Recently, Maharana et al. determined multiple structures of activated b-arrestins in complex with the The hypothesis arises that GPCR and β-arrestin-centered effector complexes vary based on subcellular Despite their contributions, these methods often lack cellular auxiliary structures and proteins. Emerging strategies incorporate unnatural amino acids and crosslinking for structural data inference Innovative structural biology techniques, pharmacological methods, state-of-the-art biosensors, supplementary

Here, we report the cryo-EM structures of an EBI2-Gi signaling complex with its endogenous agonist 7α These structures reveal an agonist binding site for the oxysterol and a potential ligand entrance site

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

Recent advances in the structure determination of GPCRs bound to different types of allosteric modulators These structural insights, together with the plethora of GPCR structures available today, will facilitate structure-based discovery and development of allosteric modulators as novel therapeutic candidates. In this review, we provide a systematic analysis of the currently available GPCR structures in complex summarize current strategies for the identification of allosteric sites as well as ligand-based and structure-based

August 2022 GPCRs steer G i and G s selectivity via TM5-TM6 switches as revealed by structures of serotonin 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 The structures reveal that transmembrane helices TM5 and TM6 alternate lengths as a macro-switch to determine We find that the macro-switch by the TM5-TM6 length is shared by class A GPCR-G protein structures.

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

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

September 2022 Structure of Mycobacterium tuberculosis Cya, an evolutionary ancestor of the mammalian Cya is an evolutionary ancestor of the mammalian membrane ACs and a model system for studies of their structure Here, we describe the cryo-EM structure of Cya bound to a stabilizing nanobody at 3.6 Å resolution. The TM helices 1–5 form a structurally conserved domain that facilitates the assembly of the helical

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

Recent advances in X-ray crystallography and cryo-EM have resulted in a wealth of GPCR structures that Here, ensemble refinement (ER) of crystallographic structures is applied to explore the impact of binding of agonists and antagonist/inverse agonists to selected structures of cannabinoid receptor 1 (CB1R),

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

Through Cryo-Electron Microscopy, authors reported the structures of four protein complexes integrated which share high sequence homology, coupled to different families of G proteins, so the comparison and structural In the same way, as in other GPCRs-G protein complexes, the structural analysis revealed that electrostatic The structural differences found between the receptor-Gs and receptor-Gi complexes evidenced that 5-HT4 Additionally, structural analysis of the TM5 and TM6 regions of 27 class A GPCRs coupled to Gs or Gi/

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

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

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

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

Here, we present cryoelectron microscopy (cryo-EM) structures of ADGRL3 in complex with Gq, Gs, Gi, and The structures reveal unique ligand-engaging mode, distinctive activation conformation, and key mechanisms The structures also reveal the uncharted structural information of GPCR/G12 coupling.

Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex The structures reveal distinctive ligand engaging model and activation conformations of GPR110. The structures also unveil the rarely explored GPCR/G12 and GPCR/G13 engagements.