A5009589316- Heat shock proteins research
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Toxin Mechanisms and Immunotoxins
- RNA Research and Splicing
- Electron Spin Resonance Studies
- Lanthanide and Transition Metal Complexes
- Advanced NMR Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Nuclear Structure and Function
- DNA and Nucleic Acid Chemistry
- Photosynthetic Processes and Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Hepatitis B Virus Studies
- Advanced MRI Techniques and Applications
- Spectroscopy and Quantum Chemical Studies
- Biochemical and Molecular Research
- DNA Repair Mechanisms
- thermodynamics and calorimetric analyses
- Signaling Pathways in Disease
- Autophagy in Disease and Therapy
- Computational Drug Discovery Methods
- Photoreceptor and optogenetics research
Tokushima University
2020-2025
Institute for Advanced Medical Research
2025
Institute of Medical Sciences
2025
Tohoku University
2023-2024
Kyoto University
2022-2023
Hokkaido University of Science
2019-2022
University of California, Berkeley
2022
Institute for Molecular Science
2022
Osaka University
2022
Tokyo University of the Arts
2022
Molecular chaperones prevent aggregation and misfolding of proteins, but scarcity structural data has impeded an understanding the recognition antiaggregation mechanisms. We report solution structure, dynamics, energetics three trigger factor (TF) chaperone molecules in complex with alkaline phosphatase (PhoA) captured unfolded state. Our show that TF uses multiple sites to bind several regions PhoA substrate protein primarily through hydrophobic contacts. Nuclear magnetic resonance (NMR)...
Aberrant phase separation- and stress granule (SG)-mediated cytosolic aggregation of TDP-43 in motor neurons is the hallmark amyotrophic lateral sclerosis (ALS). In this study, we found that graphene quantum dots (GQDs) potentially modulate during SG dynamics separation. The intrinsically disordered region C-terminus exhibited amyloid fibril formation; however, GQDs inhibited formation fibrils through direct intermolecular interactions with TDP-43. These effects were accompanied by...
Molecular chaperones alter the folding properties of cellular proteins via mechanisms that are not well understood. Here, we show Trigger Factor (TF), an ATP-independent chaperone, exerts strikingly contrasting effects on non-native as it transitions between a monomeric and dimeric state. We used NMR spectroscopy to determine atomic resolution structure 100 kDa TF. The structural data some substrate-binding sites buried in interface, explaining lower affinity for protein substrates compared...
Liquid–liquid phase separation (LLPS) of proteins and DNA has recently emerged as a possible mechanism underlying the dynamic organization chromatin. We herein report role quadruplex folding in liquid droplet formation via LLPS induced by interactions between linker histone H1 (H1), key regulator chromatin organization. Fluidity measurements inside droplets, binding assays using G-quadruplex-selective probes, structural analyses based on circular dichroism demonstrated that structures, such...
Abstract Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic deficit. However, the molecular basis for toxicity toward function as modifiers remains unidentified. Here we show that impede ability to RBPs. Isothermal titration calorimetry size-exclusion chromatography revealed...
A simple and fast nuclear magnetic resonance method for docking proteins using pseudo-contact shift (PCS) 1HN/15N chemical perturbation is presented. PCS induced by a paramagnetic lanthanide ion that attached to target protein binding peptide tag anchored at two points. provides long-range (~40 Å) distance angular restraints between the observed nuclei, while data provide loose contact-surface information. The usefulness of this was demonstrated through structure determination p62 PB1-PB1...
A nuclear magnetic resonance-based ligand screening strategy utilizing a paramagnetic lanthanide probe is presented. By fixing ion to target protein, pseudo-contact shift (PCS) and relaxation enhancement (PRE) can be observed for both the protein its bound ligand. Based on PRE PCS information, then screened from compound library structure of ligand-protein complex determined. an isotropic effect within 30 Å ion, utilized in present study. anisotropic providing long-range (~40 Å) distance...
Proper folding is essential for the biological functions of all proteins. The process intrinsically error-prone, and misfolding a polypeptide chain can cause formation toxic aggregates related to pathological outcomes such as neurodegenerative disease diabetes. Chaperones some enzymes are involved in cellular proteostasis systems that assist diminish risk aggregation. Elucidating molecular mechanisms chaperones important understanding protein misfolding- aggregation-related pathophysiology....
Abstract Meiotic prophase progression is differently regulated in males and females. In males, pachytene transition during meiotic accompanied by robust alteration gene expression. However, how expression to ensure completion remains elusive. Herein, we identify HSF5 as a male germ cell-specific heat shock transcription factor (HSF) for progression. Genetic analyzes single-cell RNA-sequencing demonstrate that essential beyond the stage under non-stress conditions rather than stress....
Pseudo contact shifts (PCSs) induced by paramagnetic lanthanide ions fixed in a protein frame provide long-range distance and angular information, are valuable for the structure determination of protein–protein protein–ligand complexes. We have been developing lanthanide-binding peptide tag (hereafter LBT) anchored at two points via bond disulfide to target proteins. However, magnetic susceptibility tensor displays symmetry, which can cause multiple degenerated solutions calculation based...
Abstract Proteins, especially multi-domain proteins, often undergo drastic conformational changes upon binding to ligands or by post-translational modifications, which is a key step regulate their function. However, the detailed mechanisms of such dynamic regulation functional processes are poorly understood because lack an efficient tool. We here demonstrate characterization MurD, 47 kDa protein enzyme consisting three domains, use solution NMR equipped with paramagnetic lanthanide probe....
Heat shock factor 1 (Hsf1), a hub protein in the stress response and cell fate decisions, senses strength, type, duration of to balance survival death through an unknown mechanism. Recently, changes physical property Hsf1 condensates due persistent have been suggested trigger apoptosis, highlighting importance biological phase separation transition decisions. In this study, mechanism underlying droplet formation oxidative was investigated 3D refractive index imaging internal architecture,...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration. Peptidylprolyl cis-trans isomerase A (PPIA) molecular chaperone involved in protein folding, and its dysfunction has been linked to ALS pathogenesis as proline recognized key residue for maintaining proper folding of ALS-related proteins. recent study identified K76E mutation PPIA sporadic patients, but effects on function structure remain unclear. In this study, we used...
Abstract A functional association is uncovered between the ribosome-associated trigger factor (TF) chaperone and ClpXP degradation complex. Bioinformatic analyses demonstrate conservation of close proximity tig , gene coding for TF, genes ClpXP, suggesting a interaction. The effect TF on ClpXP-dependent varies based nature substrate. While some substrates are slowed down or unaffected by surprisingly, increases rate third class substrates. These include λ phage replication protein λO, master...