A5006993443- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- interferon and immune responses
- RNA regulation and disease
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Liver Disease Diagnosis and Treatment
- Inflammasome and immune disorders
- Plant-Microbe Interactions and Immunity
- Plant Reproductive Biology
- Pediatric Hepatobiliary Diseases and Treatments
- Plant Molecular Biology Research
- Alkaline Phosphatase Research Studies
- Liver Disease and Transplantation
- Pericarditis and Cardiac Tamponade
- Glycosylation and Glycoproteins Research
- Sphingolipid Metabolism and Signaling
- Phosphodiesterase function and regulation
- Cholinesterase and Neurodegenerative Diseases
- Biochemical and Molecular Research
- RNA modifications and cancer
- Cardiac Structural Anomalies and Repair
- Lysosomal Storage Disorders Research
- Genetics, Aging, and Longevity in Model Organisms
- Appendicitis Diagnosis and Management
The University of Tokyo
2013-2025
Institute of Science Tokyo
2025
Kanazawa University Hospital
2024
Tokyo Medical and Dental University
2023
Chukyo Hospital
2023
Boston Children's Hospital
2020
Harvard University
2018-2020
RIKEN
2013
Funabashi Central Hospital
2013
Nagoya City University
2005
ENPP1 (Ecto-nucleotide pyrophosphatase phosphodiesterase 1), a type II transmembrane glycoprotein, hydrolyzes ATP to produce AMP and diphosphate, thereby inhibiting bone mineralization. A recent study showed that also preferentially 2'3'-cGAMP (cyclic GMP-AMP) but not its linkage isomer 3'3'-cGAMP, negatively regulates the cGAS-STING pathway in innate immune system. Here, we present high-resolution crystal structures of complex with 3'3'-cGAMP reaction intermediate pA(3',5')pG. The revealed...
Enpp1 is a membrane-bound glycoprotein that regulates bone mineralization by hydrolyzing extracellular nucleotide triphosphates to produce pyrophosphate. dysfunction causes human diseases characterized ectopic calcification. also inhibits insulin signaling, and an polymorphism associated with resistance. However, the precise mechanism which functions in these cellular processes remains elusive. Here, we report crystal structures of region mouse complex four different monophosphates, at...
The type III-E CRISPR-Cas7-11 effector binds a CRISPR RNA (crRNA) and the putative protease Csx29 catalyzes crRNA-guided cleavage. We report cryo-electron microscopy structures of Cas7-11-crRNA-Csx29 complex with without target (tgRNA), demonstrate that tgRNA binding induces conformational changes in Csx29. Biochemical experiments revealed tgRNA-dependent cleavage accessory protein Csx30 by Reconstitution system bacteria showed yields toxic fragments cause growth arrest, which is regulated...
Programmable RNA-guided DNA nucleases perform numerous roles in prokaryotes, but the extent of their spread outside prokaryotes is unclear. Fanzors, eukaryotic homolog prokaryotic TnpB proteins, have been detected genomes eukaryotes and large viruses, activity functions remain unknown. Here, we characterize Fanzors as RNA-programmable endonucleases, using biochemical cellular evidence. We found diverse that frequently associate with various transposases. Reconstruction evolution revealed...
Abstract Sperm–egg fusion is the critical step in mammalian fertilization, and requires interaction between IZUMO1 on sperm surface JUNO (also known as folate receptor (FR) 4 or IZUMO1R) egg surface. Whereas other FRs bind uptake folates, binds establishes cell–cell adhesion. However, mechanism of recognition by has remained elusive. Here we report crystal structure mouse JUNO, at 2.3 Å resolution. A structural comparison with revealed that have similar overall structures, but lacks...
Abstract In plants, leucine-rich repeat receptor-like kinases (LRR-RKs) perceive ligands, including peptides and small molecules, to regulate various physiological processes. TDIF, a member of the CLE peptide family, specifically interacts with LRR-RK TDR inhibit meristem differentiation into tracheary elements, promotes cell proliferation. Here we report crystal structure extracellular domain in complex TDIF peptide. The adopts superhelical comprising 22 LRRs, recognizes by its inner...
ADP ‐ribosylation is a conserved post‐translational protein modification that plays role in all major cellular processes, particularly DNA repair, transcription, translation, stress response and cell death. Hence, dysregulation of linked to the physiopathology several human diseases including cancers, diabetes neurodegenerative disorders. Protein can be reversed by macrodomain‐containing proteins PARG , TARG 1, MacroD1 MacroD2, which hydrolyse ester bond known link ‐ribose as well...
The detection of cytosolic DNA, derived from pathogens or host cells, by receptors is essential for appropriate immune responses. Cyclic GMP-AMP synthase (cGAS) a newly identified DNA receptor that produces cyclic GMP-AMP, which activates stimulator interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed the production type I interferons. Here we report crystal structure human cGAS. revealed cluster lysine and arginine residues forms positively charged binding surface...
Abstract Choline is an essential nutrient for all living cells and produced extracellularly by sequential degradation of phosphatidylcholine (PC). However, little known about how choline extracellularly. Here, we report that ENPP6, a choline-specific phosphodiesterase, hydrolyzes glycerophosphocholine (GPC), product PC, as physiological substrate participates in metabolism. ENPP6 highly expressed liver sinusoidal endothelial developing oligodendrocytes, which actively incorporate synthesize...
Transposon-encoded IscB family proteins are RNA-guided nucleases in the OMEGA (obligate mobile element-guided activity) system, and likely ancestors of nuclease Cas9 type II CRISPR-Cas adaptive immune system. associates with its cognate ωRNA to form a ribonucleoprotein complex that cleaves double-stranded DNA targets complementary an guide segment. Although shares RuvC HNH endonuclease domains Cas9, it is much smaller than mainly due lack α-helical nucleic-acid recognition lobe. Here, we...
RNA editing offers the opportunity to introduce either stable or transient modifications nucleic acid sequence without permanent off-target effects, but installation of arbitrary edits into transcriptome is currently infeasible. Here, we describe Programmable Editing & Cleavage for Insertion, Substitution, and Erasure (PRECISE), a versatile method writing length existing pre-mRNAs via 5' 3' trans-splicing. In trans-splicing, an exogenous template introduced compete with endogenous pre-mRNA,...
We propose the design strategy of fluorogenic probes proteases/peptidases and acylamino acid hydrolases utilizing an intramolecular O-to-N phosphoryl transfer reaction, in which main chain peptides or amino acids is retained from natural substrate but side was designed to attach fluorophore. The useful for peptidases/proteases that do not prefer modification hydrolases. have developed substrates GGT5, GGCT, PM20D1 performed screening inhibitors/activators characterize compounds modify...
Enpp1 is an extracellular membrane-bound glycoprotein that regulates bone mineralization by hydrolyzing ATP to generate pyrophosphate. The region of mouse was expressed in HEK293S GnT1(-) cells, purified using the TARGET tag/P20.1-Sepharose system and crystallized. An X-ray diffraction data set collected 3.0 Å resolution. crystal belonged space group P3(1), with unit-cell parameters a = b 105.3, c 173.7 Å. A single-wavelength anomalous dispersion (SAD) also 2.7 resolution...
Although postoperative portal vein thrombosis (PVT) is a frequent complication of splenectomy, few studies have examined PVT after simultaneous hepatectomy and splenectomy (HS). The aim this study was to clarify the risk factors for characteristics HS.
Nucleos(t)ide analogues (NAs) lead to viral suppression and undetectable hepatitis B virus (HBV) DNA in some individuals infected with HBV, but the rate of virological rebound has been unknown such patients.We examined prevalence HBV among NA-treated patients DNA.We retrospectively analyzed 303 consecutive [158 entecavir (ETV)-and 145 lamivudine (LAM)-treated] who achieved negativity, defined as < 3.7 log IU/mL for at least 3 months.They were followed up their features, including rates...
Abstract The type III-E Cas7-11 effector nuclease forms a complex with CRISPR RNA (crRNA) and the putative caspase-like protease Csx29, catalyzes crRNA-guided target cleavage, has been used for targeting in eukaryotic cells. Here, we report cryo-electron microscopy structures of Cas7-11–crRNA–Csx29 without RNA, demonstrate that binding induces conformational change Csx29 results activation. Biochemical analysis confirmed Cas7-11-bound cleaves Csx30 RNA-dependent manner. Reconstitution system...
Abstract RNA helicases and ubiquitin E3 ligases mediate many critical functions within cells, but their actions have been studied largely in distinct biological contexts. Here, we uncover evolutionarily conserved rules of engagement between tripartite motif (TRIM) that lead to functional coordination vertebrate innate immunity. Using cryo-electron microscopy biochemistry, show RIG-I-like receptors (RLRs), viral with helicase domains, interact cognate TRIM/TRIM-like through similar epitopes...
Enpp (ectonucleotide phosphodiesterase/pyrophosphatase) 6 is a membrane-bound glycoprotein that hydrolyzes choline-containing compounds such as lysophosphatidylcholine and glycerophosphorylcholine, presumably participates in choline metabolism. The catalytic domain of mouse Enpp6 was expressed HEK293T cells, purified using the TARGET tag/P20.1-Sepharose system crystallized. An X-ray diffraction data set collected to 1.8 Å resolution. crystal belonged space group P1, with unit-cell parameters...