- RNA and protein synthesis mechanisms
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Bacteriophages and microbial interactions
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- NF-κB Signaling Pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Genetics, Bioinformatics, and Biomedical Research
- CRISPR and Genetic Engineering
- Monoclonal and Polyclonal Antibodies Research
- Respiratory viral infections research
- Cytokine Signaling Pathways and Interactions
- ATP Synthase and ATPases Research
- Autophagy in Disease and Therapy
- Genetics and Neurodevelopmental Disorders
- Photoreceptor and optogenetics research
- Cholinesterase and Neurodegenerative Diseases
- Galectins and Cancer Biology
- interferon and immune responses
- Bacterial Genetics and Biotechnology
- Chemical synthesis and alkaloids
- Adenosine and Purinergic Signaling
RIKEN Center for Biosystems Dynamics Research
2020-2024
RIKEN
2017-2024
RIKEN Center for Integrative Medical Sciences
2007-2019
TagCyx Biotechnologies (Japan)
2018
Cell-free protein synthesis is a useful method for preparing proteins functional or structural analyses. However, batch-to-batch variability with regard to activity remains problem large-scale production of cell extract in the laboratory. To address this issue, we have developed novel procedure preparation bacterial high activity. The comprises cultivation using fermentor, harvesting and washing cells by tangential flow filtration, disruption high-pressure homogenizer continuous...
Rac1-bound structure and mutagenesis of the ELMO1-DOCK5 complex provide insights into how ELMO modulates DOCK activity.
Abstract The control of cell movement through manipulation cytoskeletal structure has therapeutic prospects notably in the development novel anti-metastatic drugs. In this study, we determine Ras-binding domain (RBD) ELMO1, a protein involved regulation, both alone and complex with activator RhoG verify its targetability computational nanobody design. Using our dock-and-design approach optimized native-like initial pose selection, obtain Nb01, detectable binder from scratch first-round An...
The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical viruses that are acquiring mutations. In this study, we created 494 monoclonal from patients with COVID-19-convalescent, and identified exhibited the comparable ability to clinically used in neutralization assay using pseudovirus authentic virus including variants concerns. These have different profiles various mutations, which were confirmed by...
Abstract The ten–eleven translocation (TET) protein family, consisting of three isoforms (TET1/2/3), have been found in mammalian cells and a crucial role 5‐methylcytosine demethylation genomic DNA through the catalysis oxidation reactions assisted by 2‐oxoglutarate (2OG). methylation/demethylation contributes to regulation gene expression at transcriptional level, recent studies revealed that TET1 is highly elevated malignant various diseases related alteration. inhibitors based on scaffold...
Abstract Background The discovery of glioblastoma (GBM)-initiating cells (GICs) has impacted GBM research. These are not only tumorigenic, but also exhibit resistance to radiotherapy and chemotherapy. Therefore, it is crucial characterize GICs thoroughly identify new therapeutic targets. In a previous study, we successfully identified Epithelial V-like antigen 1 (EVA1) as novel functional factor specific GICs. Methods Hybridoma were generated by immunizing BALB/c mice with EVA1-Fc fusion...
Summary Microbial rhodopsins, photoreceptor proteins widely distributed in marine microorganisms, receive large amount of light energy that sustains ecosystems. Although rhodopsins generally harbor retinal as their only chromophore, a recent study reported carotenoid antennae transfer to the proteorhodopsins, proton pump abundant environments. Here, using bacterial isolates, we detected from (myxol) not proteorhodopsin but also chloride ion-pumping rhodopsin. Carotenoid binding improved...
Acetylated lysine residues (Kac) in histones are recognized by epigenetic reader proteins, such as Yaf9, ENL, AF9, Taf14, and Sas5 (YEATS) domain-containing proteins. Human YEATS domains bind to the acetylated N-terminal tail of histone H3; however, their Kac-binding preferences at level nucleosome unknown. Through genetic code reprogramming, here, we established a core particle (NCP) array containing that were specific used it compare human domains. We found AF9-YEATS showed basal binding...
Noroviruses have been identified as major causative agents of acute nonbacterial gastroenteritis in humans. Histo-blood group antigens (HBGAs) are thought to play a role among the host cellular factors influencing norovirus infection. Genogroup I, genotype 9 (GI.9) is most recently within genogroup whose representative strain Vancouver 730 norovirus. However, molecular interactions between and GI.9 capsid protein not investigated detail. In this study, we demonstrate that preferentially...
Really interesting new gene (RING)-finger protein 52 (RNF52), an E3 ubiquitin ligase, is found in eukaryotes from yeast to humans. Human RNF52 known as breast cancer type 1 susceptibility (BRCA1)-associated 2 (BRAP or BRAP2). The central catalytic domain of BRAP comprises four subdomains: nucleotide-binding α/β plait (NBP), really (RING) zinc finger, ubiquitin-specific protease (UBP)-like finger (ZfUBP), and coiled-coil (CC). This architecture conserved orthologs; however, the domain's...
Activation of the nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) transcription factor, a central player in immune response regulation, is based on phosphorylation inhibitor kappaB alpha (IκBα) by Inhibitor kinase (IKK) that triggers IκBα degradation. Although beta (IκBβ) structurally similar to IκBα, its precise characteristics remain undefined. Herein, we report molecular interactivity IκBβ with kinase-active region IKK subunit 2 (IKK2), as well status, differs markedly...
Genetically encoded caged amino acids can be used to control the dynamics of protein activities and cellular localization in response external cues. In present study, we revealed structural basis for recognition O-(2-nitrobenzyl)-L-tyrosine (oNBTyr) by its specific variant Methanocaldococcus jannaschii tyrosyl-tRNA synthetase (oNBTyrRS), then demonstrated potential availability time-resolved X-ray crystallography. The substrate-bound crystal structure oNBTyrRS at a 2.79 Å resolution...
ABSTRACT Lipogenesis-driven metabolic flux is crucial for differentiation of pathogenic Th17 cells. Although our previous CRISPR-based screening identified PLA2G12A as a key player in this process, it has remained obscure how secreted phospholipase A 2 isoform controls differentiation. Here we show that global, T cell-specific, or fibroblast-specific deletion prevents and associated diseases including psoriasis arthritis. acts on Th17-derived extracellular vesicles (EVs) to produce...
Noroviruses are major causative agents of acute nonbacterial gastroenteritis in humans. There neither antiviral therapeutic nor vaccines for noroviruses at this time. To evaluate the potential usefulness two previously isolated human monoclonal antibody fragments, CV-1A1 and CV-2F5, we first conducted a single-particle analysis to determine cryo-electron microscopy structure virus-like particles (VLPs) from genogroup I genotype 4 (GI.4) Chiba strain uniformly coated with fragments. The...
Several antibody therapeutics have been developed against SARS-CoV-2; however, they attenuated neutralizing ability variants. In this study, we generated multiple broadly antibodies from B cells of convalescents, by using two types receptor-binding domains, Wuhan strain and the Gamma variant as bait. From 172 generated, six neutralized all strains prior to Omicron variant, five were able neutralize some sub-strains. Structural analysis showed that these a variety characteristic binding...
Summary The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical viruses that are acquiring mutations. In this study, we created 494 monoclonal from COVID-19–convalescent patients, and identified exhibited comparable ability to clinically used in the neutralization assay using pseudovirus authentic virus including variants concerns. These have different profiles various mutations, which were confirmed by...