A5027844988- Ion channel regulation and function
- Force Microscopy Techniques and Applications
- Advanced NMR Techniques and Applications
- Solid-state spectroscopy and crystallography
- Nuclear Physics and Applications
- Nanopore and Nanochannel Transport Studies
- Lipid Membrane Structure and Behavior
- Fuel Cells and Related Materials
- Nuclear physics research studies
- Mechanical and Optical Resonators
- Neuroscience and Neuropharmacology Research
- Atomic and Subatomic Physics Research
- Muon and positron interactions and applications
- Radioactive Decay and Measurement Techniques
- Integrated Circuits and Semiconductor Failure Analysis
- Electrochemical Analysis and Applications
- Mass Spectrometry Techniques and Applications
- Carbon Nanotubes in Composites
- Cardiac electrophysiology and arrhythmias
- Ion Channels and Receptors
- Neuroscience and Neural Engineering
- Particle Accelerators and Free-Electron Lasers
- Ion-surface interactions and analysis
- Photoreceptor and optogenetics research
- Superconducting Materials and Applications
Life Science Institute
2018-2024
Kanazawa University
2018-2024
Japan Science and Technology Agency
2022-2023
University of Fukui
2011-2021
Institute for Molecular Science
2006-2018
Osaka University
1999-2010
Tokyo University of Science
2007-2010
Nagoya University
2006-2008
RIKEN
2005-2006
Significance Ion selectivity is a fundamental property of ion channels. Potassium channels exhibit an unusual selectivity, allowing passage larger K + ions (ionic radius 1.3 Å) over smaller Na (1.0 Å); the mechanism underlying small rejecting remains unknown. Here, we applied as probe for examining pore prototypical potassium channel and found slight conduction across pore. traced tortuous trajectory in narrow pore, with multiple trapped here there, leading to slow elution. Contrarily,...
Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) plays a pivotal role in synaptic plasticity. It is dodecameric serine/threonine that has been highly conserved across metazoans for over million years. Despite the extensive knowledge of mechanisms underlying CaMKII activation, its behavior at molecular level remained unobserved. In this study, we used high-speed atomic force microscopy to visualize activity-dependent structural dynamics rat/hydra/ C. elegans with nanometer resolution....
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptors (AMPARs) enable rapid excitatory synaptic transmission by localizing to the postsynaptic density of glutamatergic spines. AMPARs possess large extracellular N-terminal domains (NTDs), which are crucial for AMPAR clustering at sites. However, dynamics NTDs and molecular mechanism governing their remain elusive. Here, we employed high-speed atomic force microscopy (HS-AFM) directly visualize conformational in GluA2...
Crystallographic studies of channel proteins have provided insight into the molecular mechanisms ion channels, even though these structures are obtained in absence membrane and some structural portions remained unsolved. Here we report gating structure membrane-embedded KcsA potassium using atomic force microscopy (AFM). The activation gate is located on intracellular side cytoplasmic domain was truncated to clear view this location. Once opened, individual subunits tetramer were resolved...
The mechanisms of ion permeation through potassium channels have been extensively examined. Molecular dynamics (MD) simulations demonstrated that rapidly permeating ions collide near the selectivity filter (SF) ("knock-on" mechanism), but this oversimplified mechanism is insufficient to account for experimentally observed single-channel current amplitudes. Here, we analyzed MD-simulated trajectories a Kv1.2 channel using an event-oriented analysis method, and surprisingly, found nanocavity...
Abstract The invention of 3D atomic force microscopy (3D‐AFM) has enabled visualizing subnanoscale hydration structures. Meanwhile, its applications to imaging flexible molecular chains have started be experimentally explored. However, the validity and principle such yet clarified by comparing experiments simulations or cross‐observations with an alternative technique. Such studies are impeded lack appropriate model. Here, this difficulty is overcome fabricating carbon nanotube (CNT)...
Agitoxin-2 (AgTx2) from scorpion venom is a potent blocker of K+ channels. The docking model has been elucidated, but it remains unclear whether binding dynamics are described by two-state (AgTx2-bound and AgTx2-unbound) or more complicated mechanism, such as induced fit conformational selection. Here, we observed the AgTx2 to KcsA channel using high-speed atomic force microscopy. From images repeated dissociation channel, single-molecule kinetic analyses revealed that affinity for increased...
Sodium chloride (NaCl) aqueous solution becomes NaCl hydrate, NaCl·2H2O, at low temperature, which is different from potassium and a typical complex model for studying the freeze-drying process in foods pharmaceuticals. Here, we detected unit-cell-sized particles ice as precursor substances of NaCl·2H2O during freezing by using terahertz (THz) spectroscopy. In process, Na+ Cl– ions form two types metastable on pathway to well-known crystal production, are not listed phase diagram but have...
The mechanism of the ion permeation is investigated for an anion-doped carbon nanotube, as a model K+ channel, by analyzing free energy surface and dynamics through channel. It found that main rate-determining step how enters entrance mostly blocked water molecule located at this entrance. Only about 10% ions which reach mouth channel can really enter rejection rate sensitively depends on location molecule, easily controlled charge nanotube; example, maximum obtained when anion certain...
In narrow pore ion channels, ions and water molecules diffuse in a single-file manner cannot pass each other. Under such constraints, fluxes are coupled, leading to experimentally observable phenomena as the streaming potential. Analysis of this coupled flux would provide unprecedented insights into mechanism permeation. study, permeation through KcsA potassium channel was focus, for which an eight-state discrete-state Markov model has been proposed based on crystal structure, exhibiting...
The mechanism underlying ion permeation through potassium channels still remains controversial. K+ ions permeate across a narrow selectivity filter (SF) in single file. Conventional scenarios assume that are tightly bound the SF, and, thus, they displaced from their energy well by ion-ion repulsion with an incoming ion. This tight coupling between entering and exiting has been called "knock-on" mechanism. However, this paradigm is contradicted experimental data measuring water-ion flux...
Mechanism of ion permeation through an anion-doped carbon nanotube (ANT), a model channel, is investigated. Using this system, many trajectory calculations are performed to obtain the potential energy profile, in addition free that enables separate and entropic contributions, along permeation. It found mechanism transport governed by interplay between energetic forces. The rate can be controlled changing balance these contributions with altering, for example, charge and/or length ANT, which...
Three-dimensional atomic force microscopy (3D-AFM) has resolved three-dimensional distributions of solvent molecules at solid–liquid interfaces the subnanometer scale. This method is now being extended to imaging biopolymer assemblies such as chromosomes or proteins in cells, with expectation able resolve their structures. Here, we have developed a computational simulate 3D-AFM images biopolymers by using Jarzynski equality. It found that some parts fiber structure are indeed image. The...
The β6.3-helical channel of the marine cytotoxic peptide, polytheonamide B (pTB), is examined in water, POPC bilayer, and a 1 : chloroform/methanol mixture using all-atom molecular dynamics simulations. structures fluctuations β6.3-helix pTB are investigated three environments. average structure calculated mixed solvent good agreement with NMR-resolved solvent, indicating validity parameters used for non-standard groups pTB. configuration molecules inside pore detail. It found that motions...
Atomic force microscopy (AFM) is a promising tool to visualize biomolecules at the sub-nanometer scale. Experimentally obtained AFM images have been compared with simulated ones; however, such conventional of were usually computed by calculating equidistance surface from given atomic positions, not force. Here, we use polymer model chromosome, as representative biomolecule, and probe, isoforce surfaces upon fiber. The oscillation probes utilized in dynamic mode measurements was also...
Abstract Ion transports through ion channels, biological nanopores, are essential for life: Living cells generate electrical signals by utilizing permeation channels. The measured current-voltage ( i-V ) relations most channels sublinear, however, its physical meaning is still elusive. Here we calculated the curves anion-doped carbon nanotubes, a model of an channel, using molecular dynamics simulation. It was found curve reflects origin rate-determining step: sublinear when entropy...
Abstract Divalent cation block is observed in various tetrameric ion channels. For blocking, a divalent thought to bind the pathway of channel, but such has not yet been directly observed. So, behaviour these blocking cations remains still uncertain. Here, we elucidated mechanism by reproducing effect into NavAb, well-studied sodium channel. Our crystal structures NavAb mutants show that mutations increasing hydrophilicity inner vestibule pore domain enable stack on pathway. Furthermore,...