A5100460200- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Mass Spectrometry Techniques and Applications
- Diabetes Treatment and Management
- Ion channel regulation and function
- Monoclonal and Polyclonal Antibodies Research
- Computational Drug Discovery Methods
- Chemokine receptors and signaling
- Bone health and treatments
- Aldose Reductase and Taurine
- Cytokine Signaling Pathways and Interactions
- Protist diversity and phylogeny
- Diet, Metabolism, and Disease
- Transgenic Plants and Applications
- Epigenetics and DNA Methylation
- Quantum and electron transport phenomena
- Diabetes and associated disorders
- Hormonal Regulation and Hypertension
- T-cell and B-cell Immunology
- Neuroscience and Neuropharmacology Research
- Antimicrobial Peptides and Activities
- Mechanical and Optical Resonators
- Microbial Community Ecology and Physiology
- Protein Structure and Dynamics
- Genomics and Phylogenetic Studies
Fudan University
2022-2024
Shanghai Jiao Tong University
2024
Shanghai First People's Hospital
2024
Shandong University
2021-2024
Shangrao Normal University
2024
National Center for Drug Screening
2024
Shanghai Institute of Materia Medica
2024
ShanghaiTech University
2021-2022
Second Affiliated Hospital of Zhejiang University
2021-2022
Shanghai Institute of Microsystem and Information Technology
2022
Abstract Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed maximize metabolic benefits with reduced side-effects, are in clinical trials treat type 2 diabetes obesity. To elucidate the molecular mechanisms which tirzepatide, a GIPR/GLP-1R dual agonist, peptide 20, GIPR/GLP-1R/GCGR triagonist, manifest their...
Abstract Biased signaling of G protein-coupled receptors describes an ability different ligands that preferentially activate alternative downstream pathway. In this work, we identified and characterized N-terminal truncations endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, presented three cryogenic-electron microscopy structures the CCR1–G i complex in ligand-free form bound to with a resolution 2.6–2.9 Å, illustrating structural basis natural initiates inflammation...
Abstract Chemokine receptors are a family of G-protein-coupled with key roles in leukocyte migration and inflammatory responses. Here, we present cryo-electron microscopy structures two human CC chemokine receptor–G-protein complexes: CCR2 bound to its endogenous ligand CCL2, CCR3 the apo state. The structure CCL2–CCR2–G-protein complex reveals that CCL2 inserts deeply into extracellular half transmembrane domain, forms substantial interactions receptor through most N-terminal glutamine....
Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic target, GIPR has been subjected to intensive structural studies without success. Here, we report the cryo-EM structure of human in complex with GIP G
Significance The mechanism of functional changes induced by alternative splicing GHRHR is largely unknown. Here, we demonstrate that GHRH-elicited signal bias toward β-arrestin recruitment constitutively mediated SV1. cryogenic electron microscopy structures SV1 and molecular dynamics simulations reveal the different functionalities between at near-atomic level (i.e., N termini differentiate downstream signaling pathways, G s versus β-arrestins). Our findings provide valuable insights into...
MRGPRX1, a Mas-related GPCR (MRGPR), is key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 CNF-Tx2. These reveal shallow orthosteric pocket its conformational plasticity sensing multiple different peptidic allergens. Distinct from MRGPRX2, contains unique feature at extracellular ends TM3 TM4 accommodate C-terminal "RF/RY"...
The glucagon-like peptide-1 receptor (GLP-1R) is a well-established drug target for the treatment of type II diabetes. development small-molecule positive allosteric modulators (PAMs) GLP-1R promising therapeutic strategy. Here, we report discovery and characterization PAMs with distinct chemotypes, binding to cryptic pocket formed by cytoplasmic half TM3, TM5, TM6. Molecular dynamic simulations mutagenesis studies indicate that PAM enlarges orthosteric facilitate GLP-1 binding. Further...
Cavity magnon polaritons (CMPs) are quasiparticles that combine the advantages of high-speed photons and long-lived spins. The coupling between magnons can be tuned to chiral situations by controlling microwave polarization, which is important manipulate asymmetrical energy flow for coherent signal processing. Here, strongly a mode field with controllable polarization from cross cavity, we realize flexible control CMP dynamics via effect. Such allows cavity resonance evolve into doublet or...
Subterranean karst caves are windows into the terrestrial subsurface to deconstruct dimensions of mycobiome fingerprints. However, impeded by constraints remote locations, inaccessibility specimens and technical limitations, subterranean has remained largely unknown. Weathered rock sediment samples were collected from Luohandu cave (Guilin, Southern China) subjected Illumina Hiseq sequencing ITS1 genes. A total 267 known genera 90 orders in 15 phyla revealed mycobiomes. Ascomycota dominated...
G protein-coupled receptors (GPCRs) play essential roles in numerous physiological processes and are key targets for drug development. Among them, adhesion GPCRs (aGPCRs) stand out their unique domain structures diverse functions. ADGRG2 is a member of the aGPCR family involved regulation various systems human body, including reproductive, nervous, cardiovascular, endocrine systems. Investigating antagonists enhances our understanding its regulatory processes, yet precise mechanisms action...
ABSTRACT Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor -1 (PTH1R), a member of class B G protein couple receptors (GPCRs). Both PTHrP analogs including teriparatide abaloparatide, approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report cryo-EM structures human PTH1R bound to in the protein-bound state at resolutions 2.6 3.2 Å, respectively. Detailed analysis these uncovers both common unique...
Abstract Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) the human growth hormone releasing receptor (GHRHR) is capable transducing biased signal. Differing only at N terminus, GHRHR predominantly activates s while SV1 selectively couples to β-arrestins. Based on cryo-electron microscopy structures in apo state or complex with protein, molecular dynamics simulations reveal termini and...
Abstract Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that exerts crucial metabolic functions by binding and activating its cognate receptor, GIPR. As an important therapeutic target, GIPR has been subjected to intensive structural studies without success. Here, we report the cryo-EM structure of human in complex with GIP G s heterotrimer at global resolution 2.9 Å. adopts single straight helix N terminus dipped into receptor transmembrane domain (TMD), while...
Abstract The tyrosine kinase ZAP-70 activates signals proximal to the TCR and is critical for activation of downstream signal pathways. To identify which T cell functions require activity, our lab has generated a novel mouse that expresses an analog-sensitive mutant can be inhibited specifically by analog Src family inhibitor PP1. This titratable, chemical genetic approach gives us ability rapidly inhibit activity in primary cells. We asked whether naïve effector responses upon stimulation...