- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Carbohydrate Chemistry and Synthesis
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Pharmacological Effects of Natural Compounds
- Toxin Mechanisms and Immunotoxins
- Enzyme Production and Characterization
- Enzyme Structure and Function
- Immune Cell Function and Interaction
- Alkaline Phosphatase Research Studies
- Escherichia coli research studies
- T-cell and B-cell Immunology
- Polysaccharides and Plant Cell Walls
- Cancer Research and Treatments
- Cellular transport and secretion
- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Protein Structure and Dynamics
- Signaling Pathways in Disease
- Mycobacterium research and diagnosis
- Microbial Metabolites in Food Biotechnology
Osaka University
2010-2025
Microbial Chemistry Research Foundation
2020-2025
The University of Tokyo
2018-2020
RIKEN
2013-2018
Protein Research Foundation
2008-2015
Fukushima Medical University
2013-2014
Medical & Biological Laboratories (Japan)
2014
National Institute of Advanced Industrial Science and Technology
2013
Juntendo University
2013
RIKEN Advanced Science Institute
2012
Integrin α5β1 is a major cellular receptor for the extracellular matrix protein fibronectin and plays fundamental role during mammalian development. A crystal structure of integrin headpiece fragment bound by an allosteric inhibitory antibody was determined at 2.9-Å resolution both in absence presence ligand peptide containing Arg-Gly-Asp (RGD) sequence. The antibody-bound β1 chain accommodated RGD with very limited structural changes, which may represent initial step cell adhesion mediated...
Mucosal-associated invariant T (MAIT) cells are innate-like that recognize bacterial riboflavin–based metabolites as activating antigens. Although MAIT found in tissues, it is unknown whether any host tissue–derived antigens exist. Here, we report a sulfated bile acid, cholic acid 7-sulfate (CA7S), binds the nonclassical MHC class I protein MR1 and recognized by cells. CA7S host-derived metabolite whose levels were reduced more than 98% germ-free mice. Deletion of sulfotransferase 2a family...
1,2-α-l-Fucosidase (AfcA), which hydrolyzes the glycosidic linkage of Fucα1-2Gal via an inverting mechanism, was recently isolated from Bifidobacterium bifidum and classified as first member novel glycoside hydrolase family 95. To better understand molecular mechanism this enzyme, we determined x-ray crystal structures AfcA catalytic (Fuc) domain in unliganded complexed forms with deoxyfuconojirimycin (inhibitor), 2′-fucosyllactose (substrate), l-fucose lactose (products) at 1.12-2.10Å...
Fucosyloligosaccharides have great therapeutic potential. Here we present a new route for synthesizing Fucα1,2Gal linkage by introducing glycosynthase technology into 1,2‐α‐ l ‐fucosidase. The enzyme adopts unique reaction mechanism, in which asparagine‐423 activated aspartic acid‐766 acts as base while asparagine‐421 fixes both catalytic water and glutamic acid‐566 (an acid) the proper orientations. Glycosynthase activity of N421G, N423G, D766G mutants was examined using β‐fucosyl fluoride...
Abstract N -acetylglucosaminyltransferase-V (GnT-V) alters the structure of specific -glycans by modifying α1-6-linked mannose with a β1-6-linked -acetylglucosamine branch. β1-6 branch formation on cell surface receptors accelerates cancer metastasis, making GnT-V promising target for drug development. However, molecular basis GnT-V’s catalytic mechanism and substrate specificity are not fully understood. Here, we report crystal structures human luminal domain analog. is composed GT-B fold...
Arabidopsis thaliana calcineurin B-like protein (AtCBL2) is a member of recently identified family calcium-binding proteins in A. thaliana. The crystal structure AtCBL2 has been determined at 2.1 Å resolution. forms compact α-helical with two pairs EF-hand motifs. similar overall folding topology to the structures B and neuronal calcium sensor 1, but differs significantly local conformation. ions are coordinated first fourth motifs, whereas second third motifs maintained open form by...
Polysialic acid is a linear homopolymer of α2-8-linked sialic acids attached mainly onto glycoproteins. Cell surface polysialic plays roles in cell adhesion and differentiation events manner that often dependent on the degree polymerization (DP). Anti-oligo/polysialic antibodies have DP-dependent antigenic specificity, such are widely utilized biological studies for detecting distinguishing between different oligo/polysialic acids. A murine monoclonal antibody mAb735 has unique preference...
Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are subset of CD4+ that mediate the production protective antibodies; however, SARS-CoV-2 epitopes activating Tfh not well characterized. Here, we identified and crystallized TCRs public circulating (cTfh) clonotypes expanded patients who have recovered from mild symptoms. These recognized spike (S) conserved across emerging variants. The epitope most prevalent cTfh...
The galectins are a family of beta-galactoside-binding animal lectins with conserved carbohydrate recognition domain (CRD). They have high affinity for small beta-galactosides, but binding specificity complex glycoconjugates varies considerably within the family. ligand is essential their proper function, and structures several suggested mechanism binding. Galectin-9 has two tandem CRDs short linker, we report crystal mouse galectin-9 N-terminal CRD (NCRD) in absence presence four complexes....
Galectins are a family of β-galactoside-specific lectins bearing conserved carbohydrate recognition domain. Interactions between galectins and poly-N-acetyllactosamine sequences critical in variety biological processes. Galectin-9, member the galectin family, has two domains at both N- C-terminal regions. Here we report crystal structure human galectin-9 N-terminal domain complex with N-acetyllactosamine dimers trimers. These structures revealed that can recognize internal units within...
Dendritic cell inhibitory receptor 2 (DCIR2) is a C-type lectin expressed on classical dendritic cells. We recently identified the unique ligand specificity of mouse DCIR2 (mDCIR2) toward biantennary complex-type glycans containing bisecting N-acetylglucosamine (GlcNAc). Here, we report crystal structures mDCIR2 carbohydrate recognition domain in unliganded form as well complex with an agalactosylated N-glycan unit carrying GlcNAc residue. Bisecting and α1-3 branch oligosaccharide...
Glycans normally exist as a dynamic equilibrium of several conformations. A fundamental question concerns how such molecules bind lectins despite disadvantageous entropic loss upon binding. Bisected glycan, glycan possessing bisecting N-acetylglucosamine (GlcNAc), is potentially good model for investigating conformational dynamics and glycan-lectin interactions, owing to the unique ability this sugar residue alter conformer populations thus modulate biological activities. Here we analyzed...
Phytohemagglutinin from Phaseolus vulgaris (PHA-E), a legume lectin, has an unusual specificity toward biantennary galactosylated N-glycan with bisecting N-acetylglucosamine (GlcNAc). To investigate the interaction in detail, we have solved crystal structures of PHA-E without ligand and complex derivatives. interacts trisaccharide unit (Galβ1-4GlcNAcβ1-2Man) manner completely different that mannose/glucose-specific lectins. The inner mannose residue binds to novel site on protein, its...
Asparagine-linked glycans (N-glycans) are attached onto nascent glycoproteins in the endoplasmic reticulum (ER) and subsequently processed by a set of processing enzymes ER Golgi apparatus. Accumulating evidence has shown that not all N-glycans on uniformly into mature forms (hybrid complex types mammals) through apparatus, certain remains unprocessed as an "immature" form (high-mannose type mammals). Much attention been paid to environmental factors regulating N-glycoprotein maturation,...
Protein crystallization remains one of the bottlenecks in crystallographic analysis macromolecules. An automated large-scale protein-crystallization system named PXS has been developed consisting following subsystems, which proceed parallel under unified control software: dispensing precipitants and protein solutions, sealing plates, carrying robot, incubators, observation image-storage server. A sitting-drop plate specialized for also designed developed. can set up 7680 drops vapour...