A5016645265- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Bacterial Genetics and Biotechnology
- Metabolism, Diabetes, and Cancer
- Photosynthetic Processes and Mechanisms
- Photoreceptor and optogenetics research
- Ubiquitin and proteasome pathways
- Genomics and Phylogenetic Studies
- Protein Structure and Dynamics
- Advanced Electron Microscopy Techniques and Applications
- RNA modifications and cancer
- Enzyme Structure and Function
- Chromosomal and Genetic Variations
- Connexins and lens biology
- Glycosylation and Glycoproteins Research
- Genetic diversity and population structure
- Electron and X-Ray Spectroscopy Techniques
- Cancer-related gene regulation
- Growth Hormone and Insulin-like Growth Factors
- Endoplasmic Reticulum Stress and Disease
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Cancer-related Molecular Pathways
University of Hong Kong
2023-2025
Hong Kong University of Science and Technology
2023-2025
Peking University
2010-2023
State Key Laboratory of Integrated Management of Pest Insects and Rodents
2015-2022
Chinese Academy of Sciences
1997-2022
Institute of Zoology
2015-2022
Baylor College of Medicine
2022
Institute of Molecular and Cell Biology
2022
Siberian Branch of the Russian Academy of Sciences
2022
University of Chinese Academy of Sciences
2019-2021
Methylation of histone H3 lysine-79 (H3K79) is an epigenetic mark for gene regulation in development, cellular differentiation, and disease progression. However, how this translated into downstream effects remains poorly understood owing to a lack knowledge about its readers. We developed nucleosome-based photoaffinity probe capture proteins that recognize H3K79 dimethylation (H3K79me2) nucleosomal context. In combination with quantitative proteomics approach, identified menin as H3K79me2...
The proteasome is a sophisticated ATP-dependent molecular machine responsible for protein degradation in all known eukaryotic cells. It remains elusive how conformational changes of the AAA-ATPase unfoldase regulatory particle (RP) control gating substrate-translocation channel leading to proteolytic chamber core (CP). Here we report three alternative states ATP-γ-S-bound human proteasome, which CP gates are asymmetrically open, visualized by cryo-EM at near-atomic resolutions. At least four...
The origination of new genes contributes to phenotypic evolution in humans. Two major challenges the study are inference gene ages and annotation their protein-coding potential. To tackle these challenges, we created GenTree, an integrated online database that compiles age inferences from three methods together with functional genomic data for genes. Genome-wide comparison revealed synteny-based pipeline (SBP) is most suited recently duplicated genes, whereas protein-family–based useful...
Major evolutionary transitions are enigmas, and the most notable enigma is between invertebrates vertebrates, with numerous spectacular innovations. To search for molecular connections involved, we asked whether global epigenetic changes may offer a clue by surveying inheritance reprogramming of parental DNA methylation across metazoans. We focused on gametes early embryos, where methylomes known to evolve divergently fish mammals. Here, find that methylome during embryogenesis occurs...
The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated various physiological functions. Deficiency of these would cause many diseases including hearing loss. However, their structures roles not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure mouse TMEM63C at 3.56 Å, revealed structural differences compared to TMEM63A, TMEM63B, plant orthologues...
Abstract The replisome that replicates the eukaryotic genome consists of at least three engines: Cdc45-MCM-GINS (CMG) helicase separates duplex DNA replication fork and two polymerases, one on each strand, replicate unwound DNA. Here, we determined a series cryo-electron microscopy structures yeast comprising CMG, leading-strand polymerase Polε accessory factors forked In these structures, engages or disengages with motor domains CMG by occupying alternative positions, which closely...
Significance Chemotaxis is a universal phenomenon whereby motile cells, like bacteria, navigate by following chemical gradients in their environment. Bacterial chemoreceptors can bind with specific chemoeffectors and transfer environmental signals to the cell. However, molecular mechanisms for chemoeffector binding signaling are not fully understood, rational design of bacteria respond new chemicals has been challenging. In this study, using combined experimental computational approach, we...
Abstract Bacterial chemotaxis signaling is triggered by binding of chemo-effectors to the membrane-bound chemoreceptor dimers. Though much known about structure chemoreceptors, details receptor dynamics and their effects on are still unclear. Here, using molecular simulations principle component analysis, we study periplasmic domain aspartate Tar dimer its conformational changes when different ligands (attractant, antagonist two attractant molecules). We found dominant components (modes) in...
In eukaryotes, the origin recognition complex (ORC) promotes assembly of minichromosome maintenance 2 to 7 complexes into a head-to-head double hexamer at DNA in process known as replication licensing. this study, we present series cryoelectron microscopy structures yeast ORC mutants with DNA. We show that Orc6, smallest subunit ORC, utilizes its transcription factor II B-B domain orchestrate sequential binding addition, Orc6 plays role scaffold by stabilizing basic patch (BP) Orc5 for...
Thermolysin-like proteases (TLPs), a large group of zinc metalloproteases, are synthesized as inactive precursors. TLPs with long propeptide (∼200 residues) undergo maturation following autoprocessing through an elusive molecular mechanism. We report the first two crystal structures for autoprocessed complexes typical TLP, MCP-02. In complex, Ala205 shifts upward by 33 Å from previously covalently linked residue, His204, indicating that, autocleavage peptide bond between His204 and Ala205,...
Abstract Elucidating kinetic processes of protein–protein interactions (PPI) helps to understand how basic building blocks affect overall behavior living systems. In this study, we used structure‐based properties build predictive models for constants PPI. A highly diverse PPI dataset, interaction data and structures (PPKIDS), was built. PPKIDS contains 62 with complex measured experimentally. The influence structural on kinetics studied using 35 features, describing different aspects...
Abstract Biological processes are typically actuated by dynamic multi-subunit molecular complexes. However, interactions between subunits, which govern the functions of these complexes, hard to measure directly. Here, we develop a general approach combining cryo-EM imaging technology and statistical modeling apply it study hexameric clock protein KaiC in Cyanobacteria. By clustering millions monomer images, identify two major conformational states monomers. We then classify (>160,000)...
mPGES-1 (microsomal prostaglandin E synthase-1) is a newly recognized target for the treatment of inflammatory diseases. As terminal enzyme production pathway, inhibition may have low risk side effects. Inhibitors attracted considerable attention as next-generation anti-inflammatory drugs. However, membrane protein, its enzymatic mechanism remains to be disclosed fully. We used MD (molecular dynamics) simulations, mutation analysis, hybrid experiments and co-IP (co-immunoprecipitation)...
Despite having been extensively studied, it remains largely unclear why humans bear a particularly high risk of cancer. The antagonistic pleiotropy hypothesis predicts that primate-specific genes (PSGs) tend to promote tumorigenesis, while the molecular atavism PSGs involved in tumors may represent recently derived duplicates unicellular genes. However, these predictions have not tested.
The ability of animals to perceive guidance cues from Earth's magnetic field for orientation and navigation has been supported by a wealth behavioral experiments, yet the nature this sensory modality remains fascinatingly unresolved wide open discovery. MagR proposed as putative magnetoreceptor based on its intrinsic magnetism complexation with previously suggested key protein in magnetosensing, cryptochrome, form rod-like polymer structure. Here, we report rationally designed single-chain...
To extract protein dimension and energetics information from single-molecule fluorescence resonance energy transfer spectroscopy (smFRET) data, it is essential to establish the relationship between distributions of radius gyration (<italic>R</italic><sub>g</sub>) end-to-end (donor-to-acceptor) distance (<italic>R</italic><sub>ee</sub>).