- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Plant Reproductive Biology
- Helicobacter pylori-related gastroenterology studies
- DNA Repair Mechanisms
- Plant tissue culture and regeneration
- Cellular Mechanics and Interactions
- Cardiomyopathy and Myosin Studies
- Animal Disease Management and Epidemiology
- Viral Infectious Diseases and Gene Expression in Insects
- Gastric Cancer Management and Outcomes
- Photosynthetic Processes and Mechanisms
- Bacterial Genetics and Biotechnology
- Plant Molecular Biology Research
- Virus-based gene therapy research
- Fungal and yeast genetics research
- Gastrointestinal disorders and treatments
- Microscopic Colitis
- Advanced Electron Microscopy Techniques and Applications
- Plant and animal studies
- Seed Germination and Physiology
- Chromosomal and Genetic Variations
- Plant Physiology and Cultivation Studies
University of Pennsylvania
2015-2024
Waseda University
2024
Hakodate National Hospital
2022
California University of Pennsylvania
2021
Akita University
1997-2020
Niigata City General Hospital
2020
Daiichi Sankyo (United States)
2019
Sendai University
2018
Stanford University
2010-2017
University of Colorado Denver
2017
The protein density and arrangement of subunits a complete, 32-protein, RNA polymerase II (pol II) transcription pre-initiation complex (PIC) were determined by means cryogenic electron microscopy combination chemical cross-linking mass spectrometry. PIC showed marked division in two parts, one containing all the general factors (GTFs) other pol II. Promoter DNA was associated only with GTFs, suspended above cleft not contact This structural principle underlies its conversion to...
Significance RNA polymerase II, the enzyme responsible for all mRNA synthesis in eukaryotes, requires a set of general transcription factors (GTFs) initiation transcription. A complex and GTFs, with mass 1.5 MDa, was previously isolated shown to be stable, homogeneous, active cryo-electron microscope structure at resolution 6–11 Å reported here explains requirement GTFs elucidates their roles. The recognize region gene deliver it center form amenable
Actin-related protein (Arp) 2/3 complex nucleates branched actin networks that drive cell motility. It consists of seven proteins, including two actin-related subunits (Arp2 and Arp3). Two nucleation-promoting factors (NPFs) bind Arp2/3 during activation, but the order, specific interactions, contribution each NPF to activation are unresolved. Here, we report cryo-electron microscopy structure recombinantly expressed human with WASP family NPFs bound address mechanism activation. A...
Significance In higher organisms, DNA is bound to proteins and tightly packed within the nucleus, leaving only certain regions accessible for gene expression. As enzyme RNA polymerase II (RNAPII) travels along template synthesizing RNA, it must contend with forces generated by various obstacles, some of these are known produce transient pausing even transcriptional arrest. How do organisms deal such problems? Using optical-trapping technology, we performed a single-molecule study RNAPII...
The structure of Mediator kinase module reveals its Med12-dependent Cdk8 activation mechanism and an Argonaute-like Med13 protein.
Head-to-tail polymerization of tropomyosin is crucial for its actin binding, function in filament assembly, and the regulation actin-myosin contraction. Here, we describe 2.1 A resolution structure crystals containing overlapping N C termini (TM-N TM-C) 2.9 TM-N TM-C together with a fragment troponin-T (TnT). At each junction, N-terminal helices were splayed, only one them packing against TM-C. In C-terminal region TM-C, water coiled-coil core broke local 2-fold symmetry helps generate kink...
Abstract The versatile nucleotide excision repair (NER) pathway initiates as the XPC–RAD23B–CETN2 complex first recognizes DNA lesions from genomic and recruits general transcription factor complex, TFIIH, for subsequent lesion verification. Here, we present a cryo-EM structure of an NER initiation containing Rad4–Rad23-Rad33 (yeast homologue XPC–RAD23B–CETN2) 7-subunit coreTFIIH assembled on carcinogen-DNA adduct at 3.9–9.2 Å resolution. A ~30-bp duplex could be mapped it straddles between...
Abstract Fusicoccadiene synthase from Phomopsis amygdali (PaFS) is a unique bifunctional terpenoid that catalyzes the first two steps in biosynthesis of diterpene glycoside Fusicoccin A, mediator 14-3-3 protein interactions. The prenyltransferase domain PaFS generates geranylgeranyl diphosphate, which cyclase then utilizes to generate fusicoccadiene, tricyclic hydrocarbon skeleton A. Here, we use cryo-electron microscopy show structure full-length consists central octameric core domains,...
Most eukaryotic promoter regions are divergently transcribed. As the RNA polymerase II pre-initiation complex (PIC) is intrinsically asymmetric and responsible for transcription in a single direction, it unknown how divergent arises. Here, Saccharomyces cerevisiae Mediator complexed with PIC (Med-PIC) was assembled on analyzed by cryoelectron microscopy. The structure reveals two distinct Med-PICs forming dimer through tail module, induced homodimeric activator protein localized near...
The evolutionarily conserved HIRA/Hir histone chaperone complex and ASF1a/Asf1 co-chaperone cooperate to deposit (H3/H4)
The eukaryotic Mediator, comprising a large Core (cMED) and dissociable CDK8 kinase module (CKM), regulates RNA Polymerase II (Pol II)-dependent transcription. cMED recruits Pol promotes pre-initiation complex (PIC) formation in manner inhibited by the CKM, which is also implicated post-initiation control of gene expression. Herein we report cryo-electron microscopy structures human complete Mediator its explains basis for CKM inhibition cMED-activated binds to through an intrinsically...
Structures of complete 10-subunit yeast TFIIH and a nested set subcomplexes, containing 5, 6, 7 subunits, have been determined by electron microscopy (EM) 3D reconstruction. Consistency among all the structures establishes location "minimal core" subunits (Ssl1, Tfb1, Tfb2, Tfb4, Tfb5), additional densities can be specifically attributed to Rad3, Ssl2, TFIIK trimer. These results further interpreted placement previous X-ray into give preliminary picture RNA polymerase II preinitiation...
Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is an important target in the treatment of inflammatory bowel disease (IBD). Recently, IBD with antibody to alpha4beta7-integrin, a ligand for MAdCAM-1, has been intense focus research. Our aim was clarify mechanism by which MAdCAM-1 regulated via angiotensin II type receptor (AT1R), and verify if AT1R might be novel treatment. The role expression SVEC (a murine high endothelial venule cell) MJC-1 mouse colonic examined following...