- Ion channel regulation and function
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Lipid Membrane Structure and Behavior
- Photosynthetic Processes and Mechanisms
- Cardiac electrophysiology and arrhythmias
- Mitochondrial Function and Pathology
- Signaling Pathways in Disease
- Cardiomyopathy and Myosin Studies
- ATP Synthase and ATPases Research
- Advanced Electron Microscopy Techniques and Applications
- Trace Elements in Health
- Toxin Mechanisms and Immunotoxins
- T-cell and Retrovirus Studies
- Protein Structure and Dynamics
- Immune Response and Inflammation
- Animal Disease Management and Epidemiology
- Vector-Borne Animal Diseases
- Cellular transport and secretion
- RNA Interference and Gene Delivery
- Autophagy in Disease and Therapy
- Urticaria and Related Conditions
- Immunotherapy and Immune Responses
- Microbial metabolism and enzyme function
- Circular RNAs in diseases
The University of Tokyo
1994-2024
Palo Alto Institute
1992
National Institutes of Health
1988
National Institute of Diabetes and Digestive and Kidney Diseases
1988
Soluble immunoglobulin M (IgM) forms a pentamer containing joining (J) chain polypeptide. While IgM has various immune functions, it also behaves as carrier of circulating apoptosis inhibitor macrophage (AIM; called CD5L) protein that facilitates repair during different diseases. AIM binds to the solely in presence J chain. Here, using single-particle negative-stain electron microscopy, we found exhibits an asymmetric pentagon one large gap, which is markedly from textbook symmetric model. A...
Activation of protein kinase C (PKC) in T cells leads to a variety responses including IL-2 production and receptor expression. PKC consists several isoforms that exhibit some different vitro properties. We have set up Western blotting system explore the regulation during cell activation. In Jurkat lymphoma cells, alpha, beta, delta, epsilon, zeta were detected. alpha beta existed primarily cytosol, translocated membrane fraction after 10 minutes treatment with PMA, almost completely...
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...
Abstract Xkr8–Basigin is a plasma membrane phospholipid scramblase activated by kinases or caspases. We combined cryo-EM and X-ray crystallography to investigate its structure at an overall resolution of 3.8 Å. Its membrane-spanning region carrying 22 charged amino acids adopts cuboid-like stabilized salt bridges between hydrophilic residues in transmembrane helices. Phosphatidylcholine binding was observed hydrophobic cleft on the surface exposed outer leaflet membrane. Six placed from top...
Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at plasma and organelle membranes. We herein present 2.2-3.1 Å-resolution cryo-EM structures a Golgi-localized human Zn2+/H+ antiporter ZnT7 (hZnT7) in Zn2+-bound unbound forms. Cryo-EM analyses show that hZnT7 exists as dimer via tight interactions both cytosolic transmembrane (TM) domains two protomers, each which contains single Zn2+-binding...
Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis more than 60 ligands, including those proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. Saito, Int. J. Biochem. Cell Biol. 157 , 106393 (2023)]. It expressed predominantly in renal proximal tubule epithelial cells, as well brain, lungs, eyes, inner ear, thyroid gland, placenta. also known to mediate toxic compounds, particularly that...
Cardiac ryanodine receptor (RyR2) is a large Ca2+ release channel in the sarcoplasmic reticulum and indispensable for excitation-contraction coupling heart. RyR2 activated by mutations are implicated severe arrhythmogenic diseases. Yet, structural basis underlying opening how affect remains unknown. Here, we address gating mechanism of combining high-resolution structures determined cryo-electron microscopy with quantitative functional analysis channels carrying various specific residues. We...
Cryo-EM structures of SERCA2b at 2.8- to 2.9-Å resolutions reveal how the luminal extension tail regulates its conformation.
We have identified the presence of a putative corneal wound healing substance in mouse tears, which has molecular size and immunological properties similar to those epidermal growth factor (EGF). The was capable binding EGF receptors parenchymal cells this inhibited by anti-EGF serum. concentration EGF-like tears male female mice estimated be 79.3 +/- 7.0 (SD) ng/ml 76.5 8.1 ng/ml, respectively, radioimmunoassay. Removal submandibular glands, produce large amounts EGF, reduced plasma an...
The icosahedral 60-meric porous structure of the designed supramolecular protein nanoparticle TIP60 was solved using cryo-EM.
The eyelid opening of newborn mice occurs normally on day 13.9 +/- 1.8 after birth. When were injected with anti-epidermal growth factor (EGF) antibody every other starting 1 birth, the was delayed by approximately 3 days. effect anti-EGF became less prominent as treatment started at later times: when it given from 7, no delay in observed. On hand, enhanced days EGF injection for day. This antagonized simultaneous administration antibody. present a concentration 6.6 ng/ml plasma 1-wk-old...
In a 29 year old Japanese woman with SLE, bilateral submandibular mass was detected. Computed tomographic (CT) scan suggested inflammatory changes around the glands. Histological findings of deep skin biopsy showed typical lupus erythematosus profundus (LEP). LEP should be considered in differential diagnosis an unexplained subject SLE.