Akihisa Tsutsumi

ORCID: 0000-0003-2542-4881
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About
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Research Areas
  • 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...

10.1126/sciadv.aau1199 article EN cc-by-nc Science Advances 2018-10-05

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...

10.4049/jimmunol.150.5.1746 article EN The Journal of Immunology 1993-03-01

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...

10.1038/s41467-020-19025-z article EN cc-by Nature Communications 2020-10-15

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...

10.1038/s41594-021-00665-8 article EN cc-by Nature Structural & Molecular Biology 2021-10-01

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...

10.1038/s41467-023-40521-5 article EN cc-by Nature Communications 2023-08-08

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...

10.1073/pnas.2318859121 article EN cc-by-nc-nd Proceedings of the National Academy of Sciences 2024-05-21

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...

10.1038/s41467-022-30429-x article EN cc-by Nature Communications 2022-05-20

Cryo-EM structures of SERCA2b at 2.8- to 2.9-Å resolutions reveal how the luminal extension tail regulates its conformation.

10.1126/sciadv.abb0147 article EN cc-by-nc Science Advances 2020-08-12

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...

10.1172/jci113418 article EN Journal of Clinical Investigation 1988-04-01

The icosahedral 60-meric porous structure of the designed supramolecular protein nanoparticle TIP60 was solved using cryo-EM.

10.1039/d1cc03114g article EN Chemical Communications 2021-01-01

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...

10.1152/ajpregu.1987.252.2.r376 article EN AJP Regulatory Integrative and Comparative Physiology 1987-02-01

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.

10.1177/096120339700600512 article EN Lupus 1997-06-01
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