A5046931918- Enzyme Structure and Function
- Protein Structure and Dynamics
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Ion Transport and Channel Regulation
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Glycosylation and Glycoproteins Research
- Lipid metabolism and biosynthesis
- Erythrocyte Function and Pathophysiology
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- Metabolomics and Mass Spectrometry Studies
- Microtubule and mitosis dynamics
- Neuropeptides and Animal Physiology
- Ion channel regulation and function
- RNA regulation and disease
- Calcium signaling and nucleotide metabolism
- Bacterial Genetics and Biotechnology
- Plant-Microbe Interactions and Immunity
- Legionella and Acanthamoeba research
- Legume Nitrogen Fixing Symbiosis
- Carbohydrate Chemistry and Synthesis
- Adenosine and Purinergic Signaling
Shanghai Jiao Tong University
2019-2025
Renji Hospital
2022-2025
ShanghaiTech University
2019-2024
Shanghai Ninth People's Hospital
2019-2024
State Key Laboratory of Oncogene and Related Genes
2021-2023
Chinese Academy of Sciences
2006-2019
Center for Excellence in Molecular Cell Science
2014-2019
University of Chinese Academy of Sciences
2017
Shanghai Institutes for Biological Sciences
2014-2016
University of Saskatchewan
2012-2014
Due to the lack of genetically encoded probes for fluorine-19 nuclear magnetic resonance spectroscopy (19F NMR), its utility probing eukaryotic membrane protein dynamics is limited. Here we report an efficient method genetic incorporation unnatural amino acid (UAA), 3′-trifluoromenthyl-phenylalanine (mtfF), into cannabinoid receptor 1 (CB1) in Baculovirus Expression System. The probe can be inserted at any environmentally sensitive site, while causing minimal structural perturbation target...
Abstract Phosphate, a key plant nutrient, is perceived through inositol polyphosphates (InsPs) by SPX domain-containing proteins. SPX1 an inhibit the PHR2 transcription factor to maintain Pi homeostasis. How recognizes InsP molecule and represses activation remains unclear. Here we show that, upon binding 6 , can disrupt dimers form 1:1 SPX1-PHR2 complex. The complex structure reveals that helix α1 impose steric hindrance when interacting with dimer. By stabilizing α1, allosterically...
Abstract As the major component of cell membranes, phosphatidylcholine (PC) is synthesized de novo in Kennedy pathway and then undergoes extensive deacylation-reacylation remodeling via Lands’ cycle. The re-acylation catalyzed by lysophosphatidylcholine acyltransferase (LPCAT) among four LPCAT members human, LPCAT3 preferentially introduces polyunsaturated acyl onto sn-2 position lysophosphatidylcholine, thereby modulating membrane fluidity protein functions therein. Combining x-ray...
Citrus fruit has long been considered a healthy food, but its role and detailed mechanism in lifespan extension are not clear. Here, by using the nematode C. elegans, we identified that nomilin, bitter-taste limoloid is enriched citrus, significantly extended animals' lifespan, healthspan, toxin resistance. Further analyses indicate this ageing inhibiting activity depended on insulin-like pathway DAF-2/DAF-16 nuclear hormone receptors NHR-8/DAF-12. Moreover, human pregnane X receptor (hPXR)...
Precise regulation of intracellular phosphate (Pi) is critical for cellular function, with xenotropic and polytropic retrovirus receptor 1 (XPR1) serving as the sole Pi exporter in humans. The mechanism efflux, activated by inositol pyrophosphates (PP-IPs), has remained unclear. This study presents cryo-electron microscopy structures XPR1 multiple conformations, revealing a transmembrane pathway export dual-binding activation pattern PP-IPs. A canonical binding site located at dimeric...
Oomycete pathogens such as Phytophthora secrete a repertoire of effectors into host cells to manipulate immunity and benefit infection. In this study, we found that an RxLR effector, Avr1d, promoted sojae infection in soybean hairy roots. Using yeast two-hybrid screen, identified the E3 ubiquitin ligase GmPUB13 target for Avr1d. By coimmunoprecipitation (Co-IP), gel infiltration, isothermal titration calorimetry (ITC) assays, confirmed Avr1d interacts with both vivo vitro. Furthermore,...
Constructing active heterointerfaces is powerful to enhance the electrochemical performances of transition metal dichalcogenides, but interface density regulation remains a huge challenge. Herein, MoO2 /MoS2 heterogeneous nanorods are encapsulated in nitrogen and sulfur co-doped carbon matrix (MoO2 @NSC) by controllable sulfidation. MoS2 coupled intimately at atomic level, forming with different distribution density. Strong electronic interactions triggered these for enhancing electron...
Hypophosphatasia (HPP) is a metabolic bone disease that manifests as developmental abnormalities in and dental tissues. HPP patients exhibit hypo-mineralization osteopenia due to the deficiency or malfunction of tissue non-specific alkaline phosphatase (TNAP), which catalyzes hydrolysis phosphate-containing molecules outside cells, promoting deposition hydroxyapatite extracellular matrix. Despite identification hundreds pathogenic TNAP mutations, detailed molecular pathology remains unclear....
Abstract Intraflagellar transport (IFT) trains, the polymers composed of two multi-subunit complexes, IFT-A and IFT-B, carry out bidirectional intracellular in cilia, vital for cilia biogenesis signaling. plays crucial roles ciliary import membrane proteins retrograde cargo trafficking. However, molecular architecture assembly mechanism into IFT trains vivo remains elusive. Here, we report cryo-electron microscopic structures complex from protozoa Tetrahymena thermophila . We find that...
Abstract The cell maintains its intracellular pH in a narrow physiological range and disrupting the pH-homeostasis could cause dysfunctional metabolic states. Anion exchanger 2 (AE2) works at high cellular to catalyze exchange between HCO 3 − extracellular Cl , thereby maintaining pH-homeostasis. Here, we determine cryo-EM structures of human AE2 five major operating states one transitional hybrid state. Among those states, shows inward-facing, outward-facing, intermediate conformations, as...
The proper assembly and maturation of collagens necessitate the orchestrated hydroxylation glycosylation multiple lysyl residues in procollagen chains. Dysfunctions this multistep modification process can lead to severe collagen-associated diseases. To elucidate coordination processing activities, we determine cryo-EM structures enzyme complex formed by LH3/PLOD3 GLT25D1/ColGalT1, designated as KOGG complex. Our structural analysis reveals a tetrameric comprising dimeric LH3/PLOD3s...
Adrenergic receptors are highly homologous while at the same time display a wide diversity of ligand and G-protein binding, understanding this is key for designing selective or biased drugs them. Here, we determine two crystal structures α2A adrenergic receptor (α2AAR) in complex with partial agonist an antagonist. Key non-conserved residues from ligand-binding pocket (Phe7.39 Tyr6.55) to coupling region (Ile34.51 Lys34.56) discovered play role interplay between agonism signaling α2AAR,...
The structure of human Derlin-1 reveals the mechanism misfolded protein transport across ER membrane.
Abstract Cytoplasmic incompatibility (CI) results when Wolbachia bacteria-infected male insects mate with uninfected females, leading to embryonic lethality. “Rescue” of viability occurs if the female harbors same strain. CI is caused by linked pairs genes called factors (CifA and CifB). The co-evolution CifA-CifB may account in part for patterns documented infected different strains, but molecular mechanisms remain elusive. Here, we use X-ray crystallography AlphaFold analyze from strain w...
NAD(P) has long been known as an essential energy-carrying molecule in cells. Recent data, however, indicate that also plays critical signaling roles regulating cellular functions. The crystal structure of a human protein, HSCARG, with functions previously unknown, determined to 2.4-Å resolution. reveals HSCARG can form asymmetrical dimer one subunit occupied by NADP and the other empty. Restructuring its NAD(P)-binding Rossmann fold upon binding changes extended loop α-helix restore...
The adhesion G protein–coupled receptor CD97 and its ligand complement decay-accelerating factor CD55 are important binding partners in the human immune system. Dysfunction this has been linked to disorders such as multiple sclerosis rheumatoid arthritis, well various cancers. Previous literatures have indicated that includes 3 5 epidermal growth (EGF) domains at N terminus these EGF can bind N-terminal short consensus repeat (SCR) of CD55. However, details interaction remain elusive,...
Melanocortin 4 receptor (MC4-R) antagonists are actively sought for treating cancer cachexia. We determined the structures of complexes with PG-934 and SBL-MC-31. These peptides differ from SHU9119 by substituting His6 Pro6 inserting Gly10 or Arg10. The revealed two subpockets at TM7-TM1-TM2 domains, separated N2857.36. Two peptide series based on complexed led to an antagonist activity selectivity SAR study. Most ligands retained potency, but several SBL-MC-31-derived significantly enhanced...
The adenosine A2A receptor (A2AAR) is a prototypical member of the class A subfamily G-protein-coupled receptors (GPCRs) that widely distributed in various tissues and organs human body, participates many important signal-regulation processes. We have previously summarized common activation pathway GPCRs which series conserved residues/motifs undergo conformational change during extracellular agonist binding finally induce coupling intracellular G protein. Through this mechanism we...
RNA-based fluorogenic modules have revolutionized the spatiotemporal localization of RNA molecules. Recently, a fluorophore named 5-((Z)-4-((2-hydroxyethyl)(methyl)amino)benzylidene)-3-methyl-2-((E)-styryl)-3,5-dihydro-4H-imidazol-4-one (NBSI), emitting in red spectrum, and its cognate aptamer Clivia were identified, exhibiting large Stokes shift. To explore underlying molecular basis this unique RNA-fluorophore complex, we determined tertiary structure Clivia-NBSI. The overall uses...
Abstract Anion exchanger 3 (AE3) is pivotal in regulating intracellular pH across excitable tissues, yet its structural intricacies and functional dynamics remain underexplored compared to other anion exchangers. This study unveils the insights into human AE3, including cryo-electron microscopy structures for AE3 transmembrane domains (TMD) a chimera combining N-terminal domain (NTD) with AE2 TMD (hAE3 NTD 2 ). Our analyzes reveal substrate binding site, an NTD-TMD interlock mechanism,...