A5030985240- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- Chromosomal and Genetic Variations
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- Protein Kinase Regulation and GTPase Signaling
- 14-3-3 protein interactions
- Metabolism, Diabetes, and Cancer
- Mitochondrial Function and Pathology
- Enzyme Structure and Function
- Plant nutrient uptake and metabolism
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Endoplasmic Reticulum Stress and Disease
- Protein Structure and Dynamics
- Cancer-related molecular mechanisms research
The University of Texas Southwestern Medical Center
2015-2025
Westlake University
2020-2025
He Eye Hospital
2025
He University
2025
Xi'an University of Technology
2025
Institute for Advanced Study
2020-2022
Inner Mongolia Agricultural University
2022
Howard Hughes Medical Institute
2012-2021
Morgan State University
2021
Shihezi University
2021
Solution structures of two Src homology 3 (SH3) domain-ligand complexes have been determined by nuclear magnetic resonance. Each complex consists the SH3 domain and a nine-residue proline-rich peptide selected from large library ligands prepared combinatorial synthesis. The bound adopt left-handed polyproline type II (PPII) helix, although amino to carboxyl directionalities their helices are opposite. orientation is salt bridge formed terminal arginine residues conserved aspartate-99 domain....
Cohesin is a chromosome-bound, multisubunit adenosine triphosphatase complex. After loading onto chromosomes, it generates loops to regulate chromosome functions. It has been suggested that cohesin organizes the genome through loop extrusion, but direct evidence lacking. Here, we used single-molecule imaging show recombinant human cohesin-NIPBL complex compacts both naked and nucleosome-bound DNA by extruding loops. compaction requires triphosphate (ATP) hydrolysis force sensitive. This...
The spindle assembly checkpoint mechanism delays anaphase initiation until all chromosomes are aligned at the metaphase plate. Activation of anaphase-promoting complex (APC) by binding CDC20 and CDH1 is required for exit from mitosis, APC has been implicated as a target intervention. We show that human protein hMAD2 prevents activation forming hMAD2–CDC20–APC complex. When injected into Xenopus embryos, arrests cells mitosis with an inactive APC. recombinant exists in two-folded states:...
Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins aneuploidy through integrative genomic analyses human tumors. A diverse range tumor types were found harbor deletions or inactivating mutations STAG2, gene encoding subunit cohesin complex, which regulates separation sister chromatids during cell division. Because STAG2 is on X chromosome, its inactivation requires only single mutational event. Studying...
Gene expression during mitosis During mitosis, long-range interactions within chromosomes are lost, and many enhancers become inactive. It is generally thought that gene silent at this time. However, transcription must be reactivated when cells reenter the cell cycle in order to maintain identity. Palozola et al. used a sensitive nascent RNA labeling sequencing method reveal low-level of genes mitosis. Upon mitotic exit, amplitude was reestablished with basic functions prioritized over...
Abstract The stimulator of interferon genes (STING) is an endoplasmic reticulum transmembrane protein that a target therapeutics for infectious diseases and cancer. However, early-phase clinical trials small-molecule STING agonists have shown limited antitumour efficacy dose-limiting toxicity. Here, we show polyvalent agonist—a pH-sensitive polymer bearing seven-membered ring with tertiary amine (PC7A)—activates innate-immunity pathways through the polymer-induced formation STING–PC7A...
As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion topologically entrapping DNA. How executes these fundamental transactions is not understood. Using cryo-electron microscopy (cryo-EM), we determined structure of human bound to its loader NIPBL at medium resolution. Cohesin interact extensively together form central tunnel entrap 72-base pair promote engagement cohesin's ATPase head...
How cells sense connected chromosomes Cells have a “checkpoint” that pauses cell division until all are properly arranged on the mitotic spindle to allow precise distribution of one copy each chromosome daughter cell. Hiruma et al. and Ji explain molecular mechanism by which they ready divide. The protein kinase MPS1 associates with complex at kinetochore chromosome. Its activity produces signals pause cycle. When becomes attached spindle, microtubules physically compete for binding same...
Cohesin organizes DNA into chromatids, regulates enhancer-promoter interactions, and confers sister chromatid cohesion. Its association with chromosomes is regulated by hook-shaped HEAT repeat proteins that bind Scc1, namely Scc3, Pds5, Scc2. Unlike Scc2 not a stable cohesin constituent but, as shown here, transiently replaces Pds5. Scc1 mutations compromise its interaction adversely affect cohesin's ATPase activity loading. Moreover, alter how the responds to abolish loading despite initial...
Insulin signaling controls metabolic homeostasis. Here, we report the cryo-EM structure of full-length insulin receptor (IR) and complex in active state. This unexpectedly reveals that maximally four insulins can bind 'T'-shaped IR dimer at distinct sites related by 2-fold symmetry. Insulins 1 1' to 1', formed L1 one protomer α-CT FnIII-1 other. 2 2' on each protomer. Mutagenesis cellular assays show both are required for optimal binding activation. We further identify a homotypic...
The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses thus a target coronavirus drug discovery. Nearly all inhibitors 3CLpro reported so far are covalent inhibitors. Here, we report development specific, noncovalent 3CLpro. most potent one, WU-04, effectively blocks replications in human cells with EC50 values 10-nM range. WU-04 also inhibits SARS-CoV MERS-CoV high potency, indicating that it pan-inhibitor showed anti-SARS-CoV-2...
The Src homology 3 (SH3) region is a protein domain of 55 to 75 amino acids found in many cytoplasmic proteins, including those that participate signal transduction pathways. solution structure the SH3 tyrosine kinase was determined by multidimensional nuclear magnetic resonance methods. molecule composed two short three-stranded anti-parallel beta sheets packed together at approximately right angles. Studies bound proline-rich peptide ligands revealed hydrophobic binding site on surface...