A5077511640- Microtubule and mitosis dynamics
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Cellular transport and secretion
- Hippo pathway signaling and YAP/TAZ
- Cancer therapeutics and mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Cardiomyopathy and Myosin Studies
- Autophagy in Disease and Therapy
- Cellular Mechanics and Interactions
- Nuclear Structure and Function
- Wnt/β-catenin signaling in development and cancer
- Photosynthetic Processes and Mechanisms
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Bioactive Compounds and Antitumor Agents
- Enzyme Structure and Function
- Protein Kinase Regulation and GTPase Signaling
- Heat shock proteins research
- Micro and Nano Robotics
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Protein Structure and Dynamics
- Genomics and Chromatin Dynamics
Chinese Academy of Sciences
2016-2025
Czech Academy of Sciences, Institute of Biophysics
2016-2025
Institute of Biophysics
2014-2024
University of Chinese Academy of Sciences
2014-2024
Shenzhen Institutes of Advanced Technology
2020-2024
Harbin Medical University
2024
First Affiliated Hospital of Harbin Medical University
2024
Army Medical University
2020
State Key Laboratory of Chemical Engineering
2016-2017
East China University of Science and Technology
2016-2017
Aim: Human protein disulfide isomerase (hPDI) is a key enzyme and redox-regulated chaperone responsible for oxidative folding in the endoplasmic reticulum. This work aims to reveal molecular mechanism underlying functions of hPDI by determining crystal structures different redox states. Results: The (abb′xa′) both reduced oxidized states showed that four thioredoxin domains a, b, b′, a′ are arranged as horseshoe shape with two CGHC active sites, respectively, facing each other at ends. In...
The major facilitator superfamily (MFS) is the largest family of secondary active transporters and present in all life kingdoms. Detailed structural basis substrate transport energy-coupling mechanisms these proteins remain to be elucidated. YajR a putative proton-driven MFS transporter found many Gram-negative bacteria. Here we report crystal structure Escherichia coli at 3.15 Å resolution an outward-facing conformation. In addition having 12 canonical transmembrane helices, includes unique...
Heterogeneous photocatalysis offers a promising route to realize green oxidation processes in organic synthesis. In this research, the solvent-free selective photocatalytic of benzyl alcohol benzaldehyde presence molecular oxygen was studied by using TiO2 and modified as photocatalysts. The surface modification transition metal clusters dramatically enhanced activity. Ir/TiO2 prepared photodeposition showed remarkably high activity for alcohol, an average reaction rate 14538 μmol h−1 gcat−1...
Protein-disulfide isomerase (PDI), with domains arranged as abb'xa'c, is a key enzyme and chaperone localized in the endoplasmic reticulum (ER) catalyzing oxidative folding preventing misfolding/aggregation of proteins. It has been controversial whether activity PDI redox-regulated, molecular basis unclear. Here, we show that both overall conformation human are redox-regulated. We further demonstrate conformational changes triggered by active site domain a', minimum redox-regulated cassette...
Trafficking of mitochondria into dendrites and axons plays an important role in the physiology pathophysiology neurons. Mitochondrial outer membrane protein Miro adaptor proteins TRAKs/Milton link to molecular motors. Here we show that metaxins MTX-1 MTX-2 contribute mitochondrial transport both C. elegans MTX1/2 bind MIRO-1 kinesin light chain KLC-1, forming a complex mediate kinesin-1-based movement mitochondria, which MTX-1/2 are essential accessory role. We find MTX-2, MIRO-1, TRAK-1...
Abdominal aortic aneurysm (AAA) is a lethal cardiovascular disease, and there no proven drug treatment for this condition. In study, by using the Connectivity Map (CMap) approach, we explored naringenin, naturally occurring citrus flavonoid, as putative agent inhibiting AAA. We then validated prediction with two independent mouse models of AAA, calcium phosphate (CaPO4)-induced C57BL/6J mice angiotensin II-infused ApoE-/- mice. Naringenin effectively blocked formation AAAs progression...
PDZ domain-containing scaffold protein Par-3 is the central organizer of evolutionarily conserved cell polarity-regulatory Par-3.Par-6.atypical kinase C complex. The domains have also been implicated as potential phosphoinositide signaling integrators, since its second domain binds to phosphoinositides, and third interacts with phosphatase PTEN. However, molecular basis Par-3/PTEN interaction still poorly understood. Additionally, it not known whether regulatory function PTEN in polarity...
Emerging evidence indicates that the neuronal guidance molecule SLIT plays a role in tumor suppression, as SLIT-encoding genes are inactivated several types of cancer, including lung cancer; however, it is not clear how functions cancer. Here, our data show inhibits cancer cell migration by activating RhoA and myosin 9b (Myo9b) ROBO-interacting protein suppresses activity cells. Structural analyses revealed RhoGAP domain Myo9b contains unique patch specifically recognizes RhoA. We also...
As a master regulator of the macroautophagy/autophagy-lysosomal pathway, TFEB (transcription factor EB) plays prominent role in regulating neurodegenerative diseases and cancer. The transcription activity is tightly controlled by phosphorylation dephosphorylation. Phosphorylated S211 (p-S211) can be recognized YWHA/14-3-3 proteins for cytoplasmic localization. Here, we characterized interactions between phosphorylated determined structures complex with p-S211-peptide. Although critical...
Abstract Calcium/calmodulin-dependent protein serine kinase (CASK) is a key player in vesicle transport and release neurons. However, its precise role, particularly nonneuronal systems, incompletely understood. We report that CASK functions as an important regulator of insulin secretion. depletion mouse islets/β cells substantially reduces secretion docking/fusion. forms ternary complex with Mint1 Munc18-1, this event regulated by glucose stimulation β cells. The crystal structure the...
In kinesin-3, the coiled-coil 1 (CC1) can sequester preceding neck coil (NC) for autoinhibition, but underlying mechanism is poorly understood. Here, we determined structures of uninhibited motor domain (MD)-NC dimer and inhibited MD-NC-CC1 monomer kinesin-3 KIF13B. monomer, CC1 broken into two short helices that unexpectedly interact with both NC MD. Compared MD-NC dimer, CC1-mediated integration MD not only blocks formation, also prevents linker (NL) undocking ADP release from Mutations...
Abstract WIPI proteins (WIPI1-4) are mammalian PROPPIN family phosphoinositide effectors essential for autophagosome biogenesis. In addition to phosphoinositides, can recognize a linear WIPI-interacting-region (WIR)-motif, but the underlying mechanism is poorly understood. Here, we determine structure of WIPI3 in complex with WIR-peptide from ATG2A. Unexpectedly, entwines around seven-bladed β-propeller and binds three sites blades 1–3. The N-terminal part forms short strand that augments...
Abstract Autoinhibition of kinesin-3 ensures the proper spatiotemporal control motor activity for intracellular transport, but underlying mechanism remains elusive. Here, we determine full-length structure KLP-6 in a compact self-folded state. Unexpectedly, all internal coiled-coil segments and domains cooperate to successively lock down neck domains. The first segment is melted into several short helices that work with domain restrain entire domain. second associates its neighboring FHA MBS...
Abstract Microtubules are primarily studied for the interactions of proteins that bind to their outer surfaces and ends, while regulatory mechanisms within microtubule lumen, particularly in singlet microtubules critical essential cellular processes, remain largely unexplored. Our study provides first systematic identification key single lumen. Using proximity-dependent biotin (Bio-ID) coupled with mass spectrometry, we identified candidate inner (MIPs), including Jupiter...