A5084652473- Protein Structure and Dynamics
- Advanced Proteomics Techniques and Applications
- Enzyme Structure and Function
- Bioinformatics and Genomic Networks
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- Immune responses and vaccinations
- Biotin and Related Studies
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Genetic Associations and Epidemiology
- Chemical Synthesis and Analysis
- Cancer Immunotherapy and Biomarkers
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- T-cell and B-cell Immunology
- Click Chemistry and Applications
- Machine Learning in Bioinformatics
- Immune Cell Function and Interaction
- Microbial Metabolic Engineering and Bioproduction
- Genetics, Bioinformatics, and Biomedical Research
- Ubiquitin and proteasome pathways
- Nutrition, Genetics, and Disease
- Biochemical and Structural Characterization
- Genomics and Phylogenetic Studies
Ochanomizu University
2021-2024
Tohoku University
2015-2024
Tohoku Medical Megabank Organization
2021-2024
Otsuka (Japan)
2024
Yokohama City University
2013-2018
National Institutes of Health
2011-2014
National Center for Biotechnology Information
2011-2013
Nagoya University
2009-2011
Tokyo Institute of Technology
1997-2009
Many studies have shown that missense mutations might play an important role in carcinogenesis. However, the extent to which cancer affect biomolecular interactions remains unclear. Here, we map glioblastoma on human protein interactome, model structures of affected complexes and decipher effect protein-protein, protein-nucleic acid protein-ion binding interfaces. Although some over-stabilize complexes, found overall is destabilizing, mostly affecting electrostatic component energy. We also...
The Protein Data Bank Japan (PDBj), a member of the worldwide (wwPDB), accepts and processes deposited data experimentally determined biological macromolecular structures. In addition to archiving PDB in collaboration with other wwPDB partners, PDBj also provides wide range original unique services tools, which are continuously improved updated. Here, we report new RDB Mine 2, WebGL molecular viewer Molmil, ProMode-Elastic server for normal mode analysis, virtual reality system eF-site...
Phosphorylation offers a dynamic way to regulate protein activity, subcellular localization, and stability. The majority of signaling pathways involve an extensive set protein–protein interactions, phosphorylation is widely used binding by affecting the stability, kinetics specificity interactions. Previously it was found that sites tend be located on interfaces may orthosterically modulate strength Here we studied effect in relation intrinsic disorder for different types human complexes...
Cellular fate depends on the spatiotemporal separation and integration of signaling processes that can be provided by phosphorylation events. In this study, we identify crucial points in crosstalk triggered discrete events a single target protein. We integrated data individual human phosphosites with evidence their corresponding kinases, functional consequences activity protein pathways. Our results show there is substantial fraction play critical roles between alternative redundant pathways...
Despite the advances in surface-display systems for directed evolution, variants with high affinity are not always enriched due to undesirable biases that increase target-unrelated during biopanning. Here, our goal was design a library containing improved from information of "weakly enriched" where functional were weakly enriched. Deep sequencing previous biopanning result, no antibody mimetics experimentally identified, revealed weak enrichment partly phage infection and amplification...
Germline H255Y and K508R missense mutations in the folliculin (FLCN) gene have been identified patients with bilateral multifocal (BMF) kidney tumours clinical manifestations of Birt-Hogg-Dubé (BHD) syndrome, or BMF as only manifestation; however, their impact on FLCN function remains to be determined. In order determine if promote aberrant cell proliferation leading pathogenicity, we generated mouse models expressing these mutants using BAC recombineering technology investigated ability...
Recent advances in DNA sequencing techniques have identified rare single-nucleotide variants with less than 1% minor allele frequency. Despite the growing interest and physiological importance of genome sciences, attention has been paid to frequency protein sciences. To elucidate characteristics genetic on interaction sites, from viewpoints structural position variants, we mapped about 20,000 human SNVs onto complexes. We found that are abundant interfaces, specifically core regions...
Accumulating evidence has revealed unexpected phenotypic heterogeneity and diverse functions of neutrophils in several diseases. Coronavirus disease (COVID-19) can alter the leukocyte phenotype based on severity, including neutrophil activation severe cases. However, plasticity phenotypes their relative impact COVID-19 pathogenesis not been well addressed. This study aimed to identify validate evaluate each subpopulation. We analyzed public single-cell RNA-seq, bulk proteome data from...
N-terminal acetylation is one of the most common protein modifications in eukaryotes and occurs co-translationally when N-terminus nascent polypeptide still attached to ribosome. This modification has been shown be involved a wide range biological phenomena such as half-life regulation, protein-protein protein-membrane interactions, subcellular localization. Thus, accurately predicting which proteins receive an acetyl group based on their sequence expected facilitate functional study this...
Despite similarities in their sequence and structure, there are a number of homologous proteins that adopt various oligomeric states. Comparisons these protein pairs, terms residue substitutions at the protein-protein interfaces, have provided fundamental characteristics describe how interact with each other. We prepared dataset composed pairs related different homo-oligomeric Using complexes, interface residues were identified, using structural alignments, shadow-interface been defined as...
We investigated fragmental sequences that were inserted into proteins during long molecular evolution and relevant to the association of homo-oligomers. Seventeen insertions in 12 SCOP (structure classification proteins) families examined classified large small insertions. The are composed interface-like residues effectively increase interface area. In contrast, not commonly found at interfaces have a area: their roles oligomerization process unclear. located middle protein therefore must...
Infection with SARS-CoV-2 leads to coronavirus disease 2019 (COVID-19), which can result in acute respiratory distress syndrome and multiple organ failure. However, its comprehensive influence on pathological immune responses the epithelium peripheral cells is not yet fully understood.In this study, we analyzed public scRNA-seq datasets of nasopharyngeal swabs blood investigate gene regulatory networks (GRNs) healthy individuals COVID-19 patients mild/moderate severe disease, respectively....
Functional sites on proteins play an important role in various molecular interactions and reactions between other molecules. Thus, mutations functional can severely affect the overall phenotype. Progress of genome sequencing projects has yielded a wealth information single nucleotide variants (SNVs), especially those with less than 1% minor allele frequency (rare variants). To understand influence genetic at protein level, we investigated relationship SNVs terms structural position variants....
T cell exhaustion is a state of dysfunction during chronic infection and cancer. Antibody-targeting immune checkpoint inhibitors to reverse promising approach for cancer immunotherapy. However, molecular mechanisms remain incompletely understood. Here, we performed transcriptome analysis by integrating seven datasets caused multiple diseases in both humans mice. In this study, an overlap 21 upregulated 37 downregulated genes was identified human mouse exhausted CD8+ cells. These were...
Poly-ubiquitin (poly-Ub) is involved in various cellular processes through the linkage-specific recognition of Ub-binding domains (UBD). In this study, using molecular dynamics (MD) simulation together with an enhanced sampling method, we demonstrated that K63-linked di-Ub recognizes NZF domain TAB2, a zinc finger UBD, ensemble highly dynamic structures form from weak interactions between UBD and flexible linker connecting two Ubs. However, K63 di-Ub/TAB2 complex showed much more compact...
Antibody mimetics are proteins smaller than antibodies that have antigen-binding properties. Here, we used a combination of informatic selection and experimental verification to identify from public database several candidate scaffold proteins. From those candidates, selected protein with high thermal stability, bacterial expression, mutation tolerance molecular engineering phage display techniques develop the into an antibody mimetic binding affinity for galactin-3, biomarker cancer heart...
Our study shows efficient tyrosine labeling using 1-methyl-4-arylurazole (MAUra) with laccase under mild conditions. This method achieves a high efficiency ( k cat / K m = 7.88 × 10 4 M −1 s ), selectively targeting exposed sites on proteins.
Abstract The biological functions of proteins are traditionally thought to depend on well-defined three-dimensional structures, but many experimental studies have shown that disordered regions lacking fixed structures also crucial roles. In some these regions, disorder–order transitions involved in various processes, such as protein-protein interaction and ligand binding. Therefore, it is study structural for further understanding protein folding. Owing the costs time requirements...