A5038354364- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Pharmacological Effects and Assays
- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Cancer Mechanisms and Therapy
- Mass Spectrometry Techniques and Applications
- S100 Proteins and Annexins
- Computational Drug Discovery Methods
- Chemokine receptors and signaling
- Neuroscience and Neuropharmacology Research
- Signaling Pathways in Disease
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- GDF15 and Related Biomarkers
- Ion channel regulation and function
- Diabetes Treatment and Management
- Biomarkers in Disease Mechanisms
- Neuroendocrine regulation and behavior
- interferon and immune responses
- Neuroendocrine Tumor Research Advances
- Adenosine and Purinergic Signaling
- Immune Cell Function and Interaction
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
Chinese Academy of Sciences
2013-2025
Shanghai Institute of Materia Medica
2015-2025
Abstract Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis 1–7 . An intrinsic manner activation that involves tethered agonist in the N-terminal region receptor has been proposed aGPCRs 8,9 , but its molecular mechanism remains elusive. Here we report protein-bound structures ADGRD1 ADGRF1, which exhibit many unique features with regard to...
Abstract The chemokine receptor CCR5 plays a vital role in immune surveillance and inflammation. However, molecular details that govern its endogenous recognition activation remain elusive. Here we report three cryo-electron microscopy structures of G i1 protein-coupled ligand-free state complex with the MIP-1α or RANTES, as well crystal structure MIP-1α-bound CCR5. These reveal distinct binding modes two chemokines specific accommodate pattern for distal N terminus Together functional data,...
The human formyl peptide receptor 2 (FPR2) plays a crucial role in host defense and inflammation, has been considered as drug target for chronic inflammatory diseases. A variety of peptides with different structures origins have characterized FPR2 ligands. However, the ligand-binding modes remain elusive, thereby limiting development potential drugs. Here we report crystal structure bound to potent agonist WKYMVm at 2.8 Å resolution. adopts an active conformation exhibits deep pocket....
In response to three highly conserved neuropeptides, neuropeptide Y (NPY), peptide YY, and pancreatic polypeptide (PP), four G protein-coupled receptors mediate multiple essential physiological processes, such as food intake, vasoconstriction, sedation, memory retention. Here, we report the structures of human Y1, Y2, Y4 in complex with NPY or PP, Gi1 protein. These reveal distinct binding poses upon coupling different receptors, reflecting importance conformational plasticity recognizing...
Abstract Arrestins have pivotal roles in regulating G protein-coupled receptor (GPCR) signalling by desensitizing protein activation and mediating internalization 1,2 . It has been proposed that the arrestin binds to two different conformations, ‘tail’ ‘core’, which were suggested govern distinct processes of trafficking 3,4 However, little structural information is available for tail engagement arrestins. Here we report structures glucagon (GCGR) bound β-arrestin 1 (βarr1) glucagon-bound...
Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of β amyloid Aβ42 and serves as a for humanin, that protects neuronal cells from damage by Aβ42, implying its involvement in pathogenesis Alzheimer's disease (AD). However, interaction pattern between FPR2 or humanin remains unknown. Here we report structures bound Gi N-formyl (fHN). Combined with functional data, reveal two critical regions govern recognition activity fHN, including polar binding cavity within...
As the only member of CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and neuropathy. However, drug development is hampered partially by lack structural information. Here, we present two cryo–electron microscopy structures CX3CR1-G i1 complexes ligand-free CX3CL1-bound states at 2.8- 3.4-Å resolution, respectively. Together with functional data, reveal key factors that...
Abstract Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, thus are considered targets for treating tumors. Despite great progress made therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity conspicuous side-effects. Here, we report five structures SSTR2 SSTR4 different states, including two...
Neurokinin 1 receptor (NK1R) has key regulating functions in the central and peripheral nervous systems, NK1R antagonists such as aprepitant have been approved for treating chemotherapy-induced nausea vomiting. However, lack of data on structure biochemistry limited further drug development targeting this receptor. Here, we combine NMR spectroscopy X-ray crystallography to provide dynamic static characterisation binding mode complexes with human variants. 19F-NMR showed a slow off-rate site,...
Abstract The human neuropeptide Y (NPY) 2 receptor (Y R) plays essential roles in food intake, bone formation and mood regulation, has been considered an important drug target for obesity anxiety. However, development of drugs targeting R remains challenging with no success clinical application yet. Here, we report the crystal structure bound to a selective antagonist JNJ-31020028 at 2.8 Å resolution. reveals molecular details ligand-binding mode R. Combined mutagenesis studies, provides...
Abstract Neuromedin U receptor 2 (NMU2), an emerging attractive target for treating obesity, has shown the capability in reducing food intake and regulating energy metabolism when activated. However, drug development of NMU2 was deferred partially due to lack structural information. Here, we present cryo-electron microscopy (cryo-EM) structure bound endogenous agonist NmU-25 G i1 at 3.3 Å resolution. Combined with functional computational data, reveals key factors that govern recognition...