A5101554179- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Lung Cancer Treatments and Mutations
- Brain Metastases and Treatment
- Radiopharmaceutical Chemistry and Applications
- Pharmacological Effects and Assays
- Polysaccharides and Plant Cell Walls
- Neuroscience and Neuropharmacology Research
- Immunotherapy and Immune Responses
- Diabetes Treatment and Management
- Lung Cancer Research Studies
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Probiotics and Fermented Foods
- Cancer Immunotherapy and Biomarkers
- Mass Spectrometry Techniques and Applications
- T-cell and B-cell Immunology
- Liver physiology and pathology
- Peptidase Inhibition and Analysis
- Radiomics and Machine Learning in Medical Imaging
- Esophageal Cancer Research and Treatment
- Urinary and Genital Oncology Studies
- Biomarkers in Disease Mechanisms
- PARP inhibition in cancer therapy
- Nicotinic Acetylcholine Receptors Study
Chinese Academy of Sciences
2017-2024
North China Electric Power University
2023-2024
Center for Excellence in Molecular Cell Science
2024
University of Hong Kong
2024
Beijing Institute of Technology
2023
University of Chinese Academy of Sciences
2022-2023
Qingdao University
2023
Shanghai Institute of Materia Medica
2017-2022
State Key Laboratory on Integrated Optoelectronics
2022
Jilin University
2022
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...
Choosing a partner that fits G protein–coupled receptors (GPCRs) are responsible for transducing diverse signals from outside to inside cells. This process requires specificity both in ligand binding GPCRs and coupling between their intracellular partners, proteins. Qiao et al. determined the structure of human glucagon receptor (GCGR), type B GPCR, bound one two heterotrimeric proteins, s or i1 . GCGR mainly through , structures provide basis this specificity. Conformational changes GCGR,...
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,...
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...
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...
Unimolecular dual agonists of the glucagon (GCG) receptor (GCGR) and glucagon-like peptide-1 (GLP-1R) are a new class drugs that potentially superior to GLP-1R-specific for management metabolic disease. The dual-agonist, peptide 15 (P15), is glutamic acid 16 analog GCG with GLP-1 substitutions between amino acids 17 24 has potency equivalent those cognate at GCGR GLP-1R. Here, we have used cryo-EM solve structure an active P15-GCGR-Gs complex compared this our recently published GCGR-Gs...
The prebiotic potential of exopolysaccharide (r-EPS) structures released from Lactobacillus delbrueckii ssp. bulgaricus SRFM-1 was assessed using in vitro fermentations. Fermentations with pure cultures (nine strains) and a Streptococcus strain as well two food-borne pathogenic Escherichia coli were performed. Scanning electron microscopy Congo red testing revealed that the three r-EPS fractions had different individual structures. All found to stimulate growth lactobacilli inhibit E....
Abstract Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced not available most patients who have progressed more stages at diagnosis. Patients late-onset juvenile typically present slower neurological...
ABSTRACT Although adeno-to-squamous transition (AST) has been observed in association with resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) clinic, its causality, molecular mechanism and overcoming strategies remain largely unclear. We here demonstrate that squamous occurs concomitantly TKI PC9-derived xenograft tumors. Perturbation of via DNp63 overexpression or knockdown leads significant changes responses, indicative a direct causal link between...
Semitransparent organic solar cells (STOSCs) own great potential in the building-integrated photovoltaics. The top transparent metal electrode is a crucial component to STOSCs due its functions of transmitting photons and collecting charge carriers. However, electrodes suffer from contradiction between conductivity transmittance. To solve this problem, 20 nm Ag used herein as ensure enough considerable power conversion efficiency (PCE). Furthermore, MoO3 acts optical management layer...