A5101605083- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Monoclonal and Polyclonal Antibodies Research
- Ion channel regulation and function
- Mass Spectrometry Techniques and Applications
- Biochemical Analysis and Sensing Techniques
- Protein Kinase Regulation and GTPase Signaling
- Regulation of Appetite and Obesity
- Glycosylation and Glycoproteins Research
- Chemical Synthesis and Analysis
- Chemokine receptors and signaling
- Signaling Pathways in Disease
- Hypothalamic control of reproductive hormones
- Neurotransmitter Receptor Influence on Behavior
- Lipid metabolism and disorders
- Enzyme Structure and Function
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- Antiplatelet Therapy and Cardiovascular Diseases
- Cell Adhesion Molecules Research
- Pharmacological Receptor Mechanisms and Effects
- Electromagnetic Scattering and Analysis
- Metamaterials and Metasurfaces Applications
- Protein Tyrosine Phosphatases
Zhejiang University
2019-2025
Sir Run Run Shaw Hospital
2020-2025
Ninghai First Hospital Medicare and Health Group
2025
Zhejiang Lab
2021-2024
Center for Excellence in Molecular Cell Science
2017
University of Chinese Academy of Sciences
2017
Central South University
2014
Changsha Medical University
2013
China Pharmaceutical University
2012
University of Electronic Science and Technology of China
2012
Abstract Growth hormone-releasing hormone (GHRH) regulates the secretion of growth that virtually controls metabolism and every tissue through its binding to cognate receptor (GHRHR). Malfunction in GHRHR signaling is associated with abnormal growth, making an attractive therapeutic target against dwarfism (e.g., isolated deficiency, IGHD), gigantism, lipodystrophy certain cancers. Here, we report cryo-electron microscopy (cryo-EM) structure human bound endogenous ligand stimulatory G...
Dear Editor, Dopamine acts as an essential neurotransmitter whose signaling is conducted through five G protein-coupled receptors (GPCRs), dopamine D1 to D5 (DRD1-DRD5). 1 The D1like receptors, comprising DRD1 and DRD5, primarily couple the s family of proteins activate adenylyl cyclase induce cAMP production.DRD1 most abundantly expressed receptor in CNS. It central mediating excitatory multiple dopaminergic pathways.Dysregulation has been directly linked Parkinson's disease (PD),...
Abstract G-protein-coupled receptors (GPCRs) have central roles in intercellular communication 1,2 . Structural studies revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure class-C heterodimeric GABA B receptor, which activated by inhibitory transmitter GABA, its active form complexed with i1 protein. We found that a single protein interacts GB2 subunit receptor at site mainly involves...
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....
Abstract Much effort has been invested in the investigation of structural basis G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are considered useful therapeutic agents, but molecular mechanism such ligands remains insufficiently understood. Here, we report a crystal structure ghrelin receptor bound to inverse agonist PF-05190457 and cryo-electron microscopy active receptor-Go complex endogenous ghrelin. Our structures...
Abstract Peptide hormones and neuropeptides are complex signaling molecules that predominately function through G protein-coupled receptors (GPCRs). Two unanswered questions remaining in the field of peptide-GPCR systems pertain to basis for diverse binding modes peptide ligands specificity protein coupling. Here, we report structures a neuropeptide, galanin, bound its receptors, GAL1R GAL2R, with their primary subtypes i q , respectively. The reveal unique pose which almost ‘lays flat’ on...
Abstract Follicle stimulating hormone (FSH) is an essential glycoprotein for human reproduction, which functions are mediated by a G protein-coupled receptor, FSHR. Aberrant FSH-FSHR signaling causes infertility and ovarian hyperstimulation syndrome. Here we report cryo-EM structures of FSHR in both inactive active states, with the structure bound to FSH allosteric agonist compound 21 f. The similar other receptors, highlighting conserved activation mechanism hormone-induced receptor...
Abstract Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through related receptors (GLP-1R GLP-2R) which important drug targets for metabolic disorders Crohn’s disease, respectively. Despite great progress in GLP-1R structure determination, our understanding on the differences of peptide binding signal transduction between these remains elusive. Here we report electron microscopy human GLP-2R complex with...
Structures of prostaglandin receptor EP2 revealed its agonists’ selectivity and G protein coupling mechanism.
The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through Gi2/3. Here, we firstly demonstrate that GPR156 with high constitutive activity is essential for maintaining function, and further reveal structural basis of sustained GPR156. We present cryo-EM structures human apo GPR156–Gi3 complex, unveiling small region formed by loop 2 (ECL2) N-terminus. dimer both state Gi3 protein-coupled adopt...
Phosphoinositide 3-kinases (PI3Ks) are lipid kinases essential for growth and metabolism. Their aberrant activation is associated with many types of cancers. Here we used single-particle cryoelectron microscopy (cryo-EM) to determine three distinct conformations full-length PI3Kα (p110α-p85α): the unliganded heterodimer PI3Kα, bound p110α-specific inhibitor BYL-719, exposed an activating phosphopeptide. The cryo-EM structures unbound BYL-719-bound in general accord published crystal...
The parathyroid hormone type 1 receptor (PTH1R), a class B1 G protein-coupled receptor, plays critical roles in bone turnover and Ca2+ homeostasis. Teriparatide (PTH) Abaloparatide (ABL) are terms as long-acting short-acting peptide, respectively, regarding their marked duration distinctions of the downstream signaling. However, mechanistic details remain obscure. Here, we report cryo-electron microscopy structures PTH- ABL-bound PTH1R-Gs complexes, adapting similar overall conformations yet...
Abstract Hydroxycarboxylic acids are crucial metabolic intermediates involved in various physiological and pathological processes, some of which recognized by specific hydroxycarboxylic acid receptors (HCARs). HCAR2 is one such receptor, activated endogenous β-hydroxybutyrate (3-HB) butyrate, the target for Niacin. Interest has been driven its potential as a therapeutic cardiovascular neuroinflammatory diseases. However, limited understanding how ligands bind to this receptor hindered...
G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling primary remains elusive. Histamine H
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...
Abstract The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R CCK2R act as a signaling hub in brain–gut axis, mediating digestion, emotion, memory regulation. CCK exhibit distinct preferences for ligands different posttranslational modification (PTM) states. couples to G s q , whereas primarily . Here we report the cryo-electron microscopy (cryo-EM) structures of CCK1R–G complexes liganded either by sulfated octapeptide (CCK-8) or CCK1R-selective small-molecule...