A5069786759- Protein Structure and Dynamics
- Enzyme Structure and Function
- ATP Synthase and ATPases Research
- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- Spectroscopy and Quantum Chemical Studies
- Mitochondrial Function and Pathology
- Computational Drug Discovery Methods
- DNA Repair Mechanisms
- Photosynthetic Processes and Mechanisms
- Advanced NMR Techniques and Applications
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Photoreceptor and optogenetics research
- Drug Transport and Resistance Mechanisms
- Mass Spectrometry Techniques and Applications
- RNA modifications and cancer
- Lipid Membrane Structure and Behavior
- Machine Learning in Bioinformatics
- Biochemical and Molecular Research
- Microbial Metabolic Engineering and Bioproduction
- Advanced Electron Microscopy Techniques and Applications
- Phase Equilibria and Thermodynamics
- Monoclonal and Polyclonal Antibodies Research
- Membrane-based Ion Separation Techniques
Yokohama City University
2016-2025
Life Science Institute
2017-2024
RIKEN Center for Computational Science
2021-2024
RIKEN Center for Integrative Medical Sciences
2018-2024
Naval Research Laboratory Information Technology Division
2022-2024
Tsurumi University
2018
Institute of Agrobiological Sciences
2010
RIKEN
2010
The University of Tokyo
1990-2006
Nagahama Institute of Bio-Science and Technology
2006
Abstract The coronavirus membrane protein (M) is the most abundant viral structural and plays a central role in virus assembly morphogenesis. However, process of M protein-driven are largely unknown. Here, we report cryo-electron microscopy structure SARS-CoV-2 two different conformations. forms mushroom-shaped dimer, composed transmembrane domain-swapped three-helix bundles intravirion domains. further assembles into higher-order oligomers. A highly conserved hinge region key for...
A simple formula based on linear response theory is proposed to explain and predict the structural change of proteins upon ligand binding. By regarding binding as an external perturbation, a described by atomic fluctuations in ligand-free form protein-ligand interactions. The results for three protein systems various sizes are consistent with observations crystal structures, confirming validity relationship between equilibrium
Abstract Toll-like receptor 3 (TLR3) is a member of the TLR family, which plays an important role in innate immune system and responsible for recognizing viral double-stranded RNA (dsRNA). Previous biochemical structural studies have revealed that minimum length approximately 40–50 base pairs dsRNA necessary TLR3 binding dimerization. However, efficient activation requires longer molecular mechanism underlying its length-dependent remains unknown. Here, we report cryo-electron microscopy...
Abstract A partial rigid‐body method of molecular dynamics simulations for proteins and membranes is presented. In this method, the symplectic integrator rigid bodies combined with equations motion NPT ensemble. The standard ensemble extended to membrane‐specific ensembles, NPAT (constant normal pressure lateral surface area constant temperature) NPγT tension ensembles. By more than 30‐ns aqueous hydrated lipid bilayers, results demonstrated excellent conservation total energy consistent...
Homologous recombination is an important biological process that occurs in all organisms and facilitates genome rearrangements repair of DNA double-strand breaks. Eukaryotic Rad51 proteins (Rad51 sp or Rhp51 fission yeast) are functional structural homologs bacterial RecA protein, evolutionarily conserved protein plays a key role homologous pairing strand exchange between molecules vitro . Here we show the yeast swi5 + gene, which was originally identified as gene required for normal...
Enzymatic hydrolysis of nucleotide triphosphate (NTP) plays a pivotal role in protein functions. In spite its biological significance, however, the chemistry catalysis remains obscure because complex nature reaction. Here we report study molecular mechanism adenosine (ATP) F1-ATPase, an ATP-driven rotary motor protein. Molecular simulations predicted and single-molecule observation experiments verified that rate-determining step (RDS) is proton transfer (PT) from lytic water molecule, which...
Significance Congenital muscular dystrophy (CMD) is caused by hypoglycosylation of α-dystroglycan (α-DG). In some CMD patients, mutations in the gene encoding protein O -linked mannose β1,2- N -acetylglucosaminyltransferase 1, POMGnT1 , are responsible for such hypoglycosylation. Many CMD-related genes thought to be involved glycosylation core M3, a specific -mannose–type structure α-DG. Although has long been known associated with CMD, its role M3 remains unclear. Our results reveal that...
Abstract Biological membranes play pivotal roles in the cellular activities. Transmembrane proteins are central molecules that conduct membrane-mediated biochemical functions such as signal transduction and substance transportation. Not only molecular but also supramolecular properties of transmembrane self-assembly, delocalization, orientation response essential for controlling Here we report anisotropic ligand responses a synthetic multipass ion channel. An unsymmetrical structure allows...
Inspired by mechanosensitive potassium channels found in nature, we developed a fluorinated amphiphilic cyclophane composed of rigid aromatic units connected via flexible hydrophilic octa(ethylene glycol) chains. Microscopic and emission spectroscopic studies revealed that the could be incorporated into hydrophobic layer lipid bilayer membranes self-assembled to form supramolecular transmembrane ion channel. Current recording measurements using cyclophane-containing planer successfully...
The Ornstein–Zernike integral equation (OZ equation) has been used to evaluate the distribution function of solvents around solutes, but its numerical solution is difficult for molecules with a complicated shape. This paper proposes method directly solve OZ by introducing 3D lattice. employs no approximation reference interaction site model (RISM) employed. enables one obtain spatial spherical solutes an arbitrary Numerical accuracy sufficient when grid-spacing less than 0.5 Å solvent water....
Hydrophobic effects in aqueous urea were analyzed by molecular dynamics simulations. The contribution of solvents to the potential mean force between two methane molecules was calculated using simulations and compared with solubility data hydrocarbons urea. Both simulation results indicated that stabilizes methane-methane association. stabilization due increasing solvation free energies small such as addition larger hydrocarbons, on other hand, are decreased This effect solute size...
Post-translational modification by small ubiquitin-like modifier (SUMO) proteins has been implicated in the regulation of a variety cellular events. The functions sumoylation are often mediated downstream effector harboring SUMO-interacting motifs (SIMs) that composed hydrophobic core and stretch acidic residues. MBD1-containing chromatin-associated factor 1 (MCAF1), transcription repressor, interacts with SUMO-2/3 SUMO-1, preference for SUMO-2/3. We used NMR spectroscopy to solve solution...
The configurational entropy of solute molecules is a crucially important quantity to study various biophysical processes. Consequently, it necessary establish an efficient quantitative computational method calculate as accurately possible. In the present paper, we investigate performance quasi-harmonic and related methods, including widely used methods implemented in popular molecular dynamics (MD) software packages, compared with Clausius method, which capable computing change upon...
Abstract Toll-like receptor 7 (TLR7) recognizes both microbial and endogenous RNAs nucleosides. Aberrant activation of TLR7 has been implicated in several autoimmune diseases including systemic lupus erythematosus (SLE). Here, by modifying potent agonists, we develop a series TLR7-specific antagonists as promising therapeutic agents for SLE. These compounds protect mice against lethal autoimmunity. Combining crystallography cryo-electron microscopy, identify the open conformation reveal...
Aquaglyceroporins such as aquaporin−3 (AQP3) and its bacterial homologue GlpF facilitate water glycerol permeation across lipid bilayers. X-ray crystal structures of showed open pore conformations, AQP3 has also been predicted to adopt this conformation. Here we present cryo-electron microscopy rat in different narrowed conformations. In n-dodecyl-β-D-maltopyranoside detergent micelles, aromatic/arginine constriction filter residues containing Tyr212 form a 2.8-Å diameter pore, whereas...
Molecular dynamics simulations were performed for four members of the aquaporin family (AQP1, AQPZ, AQP0, and GlpF) in explicit membrane environment. The single‐channel water permeability, p f , was evaluated to be GlpF ∼ AQPZ > AQP1 ≫ while their relative pore sizes AQP0. This relation between size indicates that permeability determined not only by channel radius, but also another competing factor. Analysis revealed this factor single‐file nature transport.
Thermostable direct hemolysin (TDH) is a major virulence factor of Vibrio parahaemolyticus that causes pandemic foodborne enterocolitis mediated by seafood. TDH exists as tetramer in solution, and it possesses extreme hemolytic activity. Here, we present the crystal structure at 1.5 A resolution. The forms central pore with dimensions 23 diameter approximately 50 depth. Pi-cation interactions between protomers comprising were indispensable for activity TDH. N-terminal region was...
The multidrug transporter AcrB transports a broad range of drugs out the cell by means proton-motive force. asymmetric crystal structure trimeric suggests functionally rotating mechanism for drug transport. Despite various supportive forms evidence from biochemical and simulation studies this mechanism, link between functional rotation proton translocation across membrane remains elusive. Here, calculating minimum free energy pathway complete trimer, we describe structural energetic basis...
Ionic scattering factors of atoms that compose biological molecules have been computed by the multi-configuration Dirac–Fock method. These ions are chemically unstable and their had not reported except for O − . Yet these required estimation partial charges in protein nucleic acids. The electron particularly important as curves vary considerably between neutral charged spatial-resolution range explored structural biology. calculated X-ray then parameterized major curve models used...
Antibody labeling has been conducted extensively for structure determination using both X-ray crystallography and electron microscopy (EM). However, establishing target-specific antibodies is a prerequisite applying antibody-assisted structural analysis. To expand the applicability of this strategy, an alternative method developed to prepare antibody complex by inserting exogenous epitope into target. It already demonstrated that Fab NZ-1 monoclonal can form stable with target containing...
The roles of hydrogen bonding and the hard core water on hydrophobic hydration are clarified using Monte Carlo simulation test particle method to compare cavity formation in with that a Lennard-Jones (LJ) fluid same molecular size density. Similarities differences two fluids examined terms free energy, energy change, change coordination number upon formation. at given density decrease around cavities similar those LJ fluid. These similarities due geometrical restriction molecules. effect can...