A5022470629- Seismic Waves and Analysis
- Earthquake Detection and Analysis
- Methane Hydrates and Related Phenomena
- RNA and protein synthesis mechanisms
- Growth Hormone and Insulin-like Growth Factors
- RNA modifications and cancer
- Material Dynamics and Properties
- RNA Research and Splicing
- Enzyme Structure and Function
- Estrogen and related hormone effects
- DNA and Nucleic Acid Chemistry
- Seismology and Earthquake Studies
- Bacteriophages and microbial interactions
- Thermodynamic properties of mixtures
- Receptor Mechanisms and Signaling
- Biochemical and Molecular Research
- Bacterial Genetics and Biotechnology
- Prostate Cancer Treatment and Research
- Monoclonal and Polyclonal Antibodies Research
- Cholesterol and Lipid Metabolism
- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
- SARS-CoV-2 and COVID-19 Research
- Advanced Electron Microscopy Techniques and Applications
- Photosynthetic Processes and Mechanisms
Case Western Reserve University
2016-2025
Wuhan University
2024
University School
2019-2024
Zhongnan Hospital of Wuhan University
2024
Jilin Academy of Agricultural Sciences
2021-2023
Guangxi University of Chinese Medicine
2023
National Institutes of Health
2002-2022
Education Department of Heilongjiang Province
2022
Harbin Medical University
2022
Sichuan University
2022
Impairment of protein phosphatases, including the family serine/threonine phosphatases designated PP2A, is essential for pathogenesis many diseases, cancer. The ability PP2A to dephosphorylate hundreds proteins regulated by over 40 specificity-determining regulatory "B" subunits that compete assembly and activation heterogeneous heterotrimers. Here, we reveal how a small molecule, DT-061, specifically stabilizes B56α-PP2A holoenzyme in fully assembled, active state selective substrates, such...
Sperm motility is crucial to reproductive success in sexually reproducing organisms. Impaired sperm movement causes male infertility, which increasing globally. are powered by a microtubule-based molecular machine—the axoneme—but it unclear how axonemal microtubules ornamented support diverse fertilization environments. Here, we present high-resolution structures of native doublet (DMTs) from sea urchin and bovine sperm, representing external internal fertilizers. We identify >60 proteins...
Abstract Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of axoneme available for alga Chlamydomonas reinhardtii 1 , structures mammalian axonemes are incomplete 1–5 . Furthermore, we do not fully understand how vary across motile-ciliated cell types in body. Here use cryoelectron microscopy, tomography proteomics to resolve 96-nm modular repeat axonemal...
Previously, we reported that fluid-phase endocytosis of native LDL by PMA-activated human monocytederived macrophages converted these into cholesterol-enriched foam cells (Kruth, H. S., Huang, W., Ishii, I., and Zhang, W. Y. (2002) J. Biol. Chem. 277, 34573-34580). Uptake fluid can occur either micropinocytosis within vesicles (<0.1 μm diameter) or macropinocytosis vacuoles (∼0.5-5.0 μm) named macropinosomes. The current investigation has identified as the pathway for determined signaling...
The recently developed GROMOS 54A7 force field, a modification of the 53A6 is validated by simulating folding equilibrium two β-peptides which show different dominant folds, i.e., 314-helix and hairpin, using three fields, 45A3, 53A6, 54A7. field stabilizes both agreement simulated NOE atom–atom distances with experimental NMR data slightly improved when while 3J couplings results remains essentially unchanged varying field. to improve stability α-helical structures in proteins can thus be...
Abstract Serotonin receptors (5-HT 3A R) directly regulate gut movement, and drugs that inhibit 5-HT R function are used to control emetic reflexes associated with gastrointestinal pathologies cancer therapies. The involves a finely tuned orchestration of three domain movements include the ligand-binding domain, pore intracellular domain. Here, we present structure from full-length channel in apo-state determined by single-particle cryo-electron microscopy at nominal resolution 4.3 Å. In...
Interventions against variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Stable and potent nanobodies (Nbs) that target the receptor binding domain (RBD) SARS-CoV-2 spike promising therapeutics. However, it is unknown if Nbs broadly neutralize circulating variants. We found RBD highly resistant to concern (VOCs). High-resolution cryoelectron microscopy determination eight Nb-bound structures reveals multiple neutralizing epitopes clustered into...
The glucagon-like peptide-1 (GLP-1) receptor is a validated drug target for metabolic disorders. Ago-allosteric modulators are capable of acting both as agonists on their own and efficacy enhancers orthosteric ligands. However, the molecular details ago-allosterism remain elusive. Here, we report three cryo-electron microscopy structures GLP-1R bound to (i) compound 2 (an ago-allosteric modulator); (ii) GLP-1; (iii) LY3502970 (a small molecule agonist), all in complex with heterotrimeric Gs....
Abstract Mitochondrial fission is a critical cellular event to maintain organelle function. This multistep process initiated by the enhanced recruitment and oligomerization of dynamin-related protein 1 (Drp1) at surface mitochondria. As such, Drp1 essential for inducing mitochondrial division in mammalian cells, homologous proteins are found all eukaryotes. member dynamin superfamily (DSPs), controlled self-assembly into large helical polymers stimulates its GTPase activity promote membrane...
This investigation has elucidated a mechanism for development of macrophage foam cells when macrophages are incubated with native low density lipoprotein (LDL). LDL is believed to be the main source cholesterol that accumulates in monocyte-derived within atherosclerotic plaques, but not previously been shown cause substantial accumulation macrophages. We have found activation human phorbol 12-myristate 13-acetate (PMA) stimulates uptake and degradation acyl-CoA:cholesterol...
Acinetobacter baumannii is a successful human pathogen which has emerged as one of the most problematic and highly antibiotic-resistant Gram-negative bacteria worldwide. Multidrug efflux major mechanism that A. uses to counteract action multiple classes antibiotics, such β-lactams, tetracyclines, fluoroquinolones, aminoglycosides. Here, we report cryo-electron microscopy (cryo-EM) structure prevalent AdeB multidrug pump, indicates plausible pathway for extrusion. Overall, our data suggest...
Vaccine boosters and infection can facilitate the development of SARS-CoV-2 antibodies with improved potency breadth. Here, we observe superimmunity in a camelid extensively immunized receptor-binding domain (RBD). We rapidly isolate large repertoire specific ultra-high-affinity nanobodies that bind strongly to all known sarbecovirus clades using integrative proteomics. These pan-sarbecovirus (psNbs) are highly effective against SARS-CoV variants, including Omicron, best median...
Cystic fibrosis (CF) is a fatal, autosomal, recessive genetic disease that characterized by profound lung inflammation. The inflammatory process believed to be caused massive overproduction of the proinflammatory protein IL-8, and high levels IL-8 in CF are therefore central mechanism behind pathophysiology. We show here digitoxin, at sub nM concentrations, can suppress hypersecretion from cultured epithelial cells. Certain other cardiac glycosides also active but with much less potency....
The transactivator protein of human T-lymphotropic virus type I (HTLV-I), Tax, forms multiprotein complexes with the ubiquitous transcription factor CREB and CREB/ATF-1 heterodimer. interaction between Tax is highly specific results in increased binding Tax/CREB to HTLV-I 21-bp repeats. Despite extensive sequence similarities ATF-1, interacts ATF-1 only marginally. Compared CREB, exhibits greatly DNA recognition specificity preferentially assembles on a consensus site,...
Using time-resolved nonlinear dielectric relaxation measurements at fields as high 450 kV/cm, the nonthermal effects of energy absorption are studied for simple and associating polar liquids in their supercooled state. The experiment is a low frequency analog microwave heating facilitates tracking flow time, it accumulates slow degrees freedom transfers eventually to vibrational heat bath liquid. Most findings agree with phenomenological model heterogeneous regarding structure...
Heating samples by microwave radiation is a particular example of the more general phenomenon where materials absorb energy from an external time-dependent field electric, magnetic, or mechanical nature. How this compares with conventional heating question continued interest. Here, we show that origin absorptivity determines whether accumulates in slower configurational degrees freedom transfers rapidly to phonon bath, only latter situation equivalent heating. Based upon time-resolved...
Abstract Human estrogen receptor alpha (hERα) is a hormone-responsive nuclear (NR) involved in cell growth and survival that contains both DNA-binding domain (DBD) ligand-binding (LBD). Functionally relevant inter-domain interactions between the DBD LBD have been observed several other NRs, but for hERα, detailed structural architecture of complex unknown. By utilizing integrated complementary techniques small-angle X-ray scattering, hydroxyl radical protein footprinting computational...
Type I interferons (IFN-I) protect us from viral infections. Signal transducer and activator of transcription 2 (STAT2) is a key component interferon-stimulated gene factor 3 (ISGF3), which drives expression in response to IFN-I. Using electron microscopy, we found that, naive cells, U-STAT2, lacking the activating tyrosine phosphorylation, forms heterodimer with U-STAT1 an inactive, anti-parallel conformation. A novel phosphorylation STAT2 on T404 promotes IFN-I signaling by disrupting...
The arginyl-transferase ATE1 is a tRNA-dependent enzyme that covalently attaches an arginine molecule to protein substrate. Conserved from yeast humans, deficiency in mice correlates with defects cardiovascular development and angiogenesis results embryonic lethality, while conditional knockouts exhibit reproductive, developmental, neurological deficiencies. Despite the recent revelation of tRNA binding mechanism catalytic cycle ATE1, structure-function relationship higher organisms not well...
<p>Supp Figure 5</p>
<p>Supp Figure 11</p>