A5103095017- Cellular Mechanics and Interactions
- Force Microscopy Techniques and Applications
- Cardiomyopathy and Myosin Studies
- Advanced Fluorescence Microscopy Techniques
- DNA Repair Mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Circular RNAs in diseases
- Bacterial Genetics and Biotechnology
- Protist diversity and phylogeny
- Microtubule and mitosis dynamics
- Electron and X-Ray Spectroscopy Techniques
- Extracellular vesicles in disease
- Fungal and yeast genetics research
- Photosynthetic Processes and Mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Antibiotic Resistance in Bacteria
- Biotin and Related Studies
- Cancer-related molecular mechanisms research
- Kruppel-like factors research
- Cell Adhesion Molecules Research
- Bacteriophages and microbial interactions
- 3D Printing in Biomedical Research
- MicroRNA in disease regulation
- Vibrio bacteria research studies
- Heat shock proteins research
Eastern Virginia Medical School
2014-2024
University of Virginia
2004-2014
University of California, Davis
2008
University of California, Los Angeles
2004-2006
Albert Einstein College of Medicine
2006
Cancer Research UK
2005
University of Iowa
2004
Moscow State University
2002
Lomonosov Moscow State University
2002
Institute of Cytology
2000-2001
Proteins in the actin depolymerizing factor (ADF)/cofilin family are essential for rapid F-actin turnover, and most depolymerize a pH-dependent manner. Complexes of human plant ADF with at different pH were examined using electron microscopy novel method image analysis helical filaments. Although changes mean twist actin, we show that it does this by stabilizing preexisting angular conformation. In addition, induces large (∼12°) tilt subunits high where filaments readily disrupted. A second...
Organogenesis and tumor metastasis involve the transformation of epithelia to highly motile mesenchymal-like cells. Septins are filamentous G proteins, which overexpressed in metastatic carcinomas, but their functions epithelial motility unknown. Here, we show that a novel network septin filaments underlies organization transverse arc radial (dorsal) stress fibers at leading lamella migrating renal epithelia. Surprisingly, depletion resulted smaller more transient peripheral focal adhesions....
The isolation and subsequent molecular analysis of extracellular vesicles (EVs) derived from patient samples is a widely used strategy to understand vesicle biology facilitate biomarker discovery. Expressed prostatic secretions in urine are tumor proximal fluid that has received significant attention as source potential prostate cancer (PCa) biomarkers for use liquid biopsy protocols. Standard EV methods like differential ultracentrifugation (dUC) co-isolate protein contaminants mask...
Germ-line mutations in BRCA2 account for approximately half the cases of autosomal dominant familial breast cancers. has been shown to interact directly with RAD51, an essential component cellular machinery homologous recombination and maintenance genome stability. Interactions between RAD51 take place by means conserved BRC repeat regions BRCA2. Previously, it was that peptides corresponding BRC3 or BRC4 bind monomers block RAD51–DNA filament formation. In this work, we further analyze...
Many actin binding proteins have a modular architecture, and calponin-homology (CH) domains are one such structurally conserved module found in numerous that interact with F-actin. The manner which CH-domains bind F-actin has been controversial. Using cryo-EM single-particle approach to helical reconstruction, we generated 12-Å-resolution maps of alone decorated fragment human fimbrin (L-plastin) containing tandem CH-domains. high resolution allows an unambiguous fit the crystal structure...
It has been widely assumed that the atomic structure of flagellar filament from Salmonella typhimurium serves as a model for all bacterial filaments given sequence conservation in coiled-coil regions responsible polymerization. On basis electron microscopic images, we show Campylobacter jejuni have seven protofilaments rather than 11 S. . The vertebrate Toll-like receptor 5 (TLR5) recognizes region flagellin is involved subunit-subunit assembly and many other pathogenic bacteria, this short...
Like many bacterial pathogens, Salmonella spp. use a type III secretion system to inject virulence proteins into host cells. The invasion protein A (SipA) binds actin, enhances its polymerization near adherent extracellular bacteria, and contributes cytoskeletal rearrangements that internalize the pathogen. By combining x-ray crystallography of SipA with electron microscopy image analysis SipA-actin filaments, we show functions as "molecular staple," in which globular domain two nonglobular...
Proteins in the ADF/cofilin (AC) family are essential for rapid rearrangements of cellular actin structures. They have been shown to be active both severing and depolymerization filaments vitro, but detailed mechanism action is not known. Under vitro conditions, subunits filament can treadmill; with hydrolysis ATP driving addition at one end loss from opposite end. We used electron microscopy image analysis show that AC molecules effectively disrupt longitudinal contacts between protomers...
Troponin C (TnC) is the Ca2+-sensing subunit of troponin that responsible for activating thin filaments in striated muscle, and turn regulating systolic diastolic contractile function cardiac muscle. Secondary structure vertebrate TnC mainly α-helices, with 9 helices named from N A-H. The N-helix a 12-residue-long α-helix located at extreme amino terminus protein only helical does not participate forming Ca2+-binding EF-hands. Evolutionarily, found mammalian species most other vertebrates...
Utrophin, like its homologue dystrophin, forms a link between the actin cytoskeleton and extracellular matrix. We have used new method of image analysis to reconstruct filaments decorated with actin-binding domain utrophin, which contains two calponin homology domains. find different modes binding, either one or calponin-homology (CH) domains bound per subunit, these are also distinguishable by their very effects on F-actin rigidity. Both involve an extended conformation CH domains, as...
Mutations in BRCA2 predispose individuals to breast cancer, a consequence of the role DNA repair. Human interacts with recombinase RAD51 via eight BRC repeats. Controversy has existed, however, about whether interactions are primarily monomers or RAD51-DNA helical polymer, and there is single interaction multiple ones. We show here that motif Caenorhabditis elegans homolog, CeBRC-2, contains two different RAD-51-binding regions. One these regions binds only weakly RAD-51-DNA filaments but...
Most bacterial chromosomes contain homologs of plasmid partitioning ( par ) loci. These loci encode ATPases called ParA that are thought to contribute the mechanical force required for chromosome and segregation. In Vibrio cholerae , II (chrII) locus is essential chrII Here, we found purified ParA2 had ATPase activities comparable other homologs, but, unlike many did not form high molecular weight complexes in presence ATP alone. Instead, formation polymers DNA. Electron microscopy...
Actin, one of the most highly conserved and abundant eukaryotic proteins, is constantly being polymerized depolymerized within cells as part cellular motility, tissue formation repair, embryonic development. Many proteins exist that bind to monomeric or filamentous (F) forms actin regulate polymerization state. It has become increasingly apparent ability different filament dynamics depends on in altered conformations. Yet, little known about how these conformational changes occur at...
Abstract Prostate cancer afflicts 1 in 7 men and is the second leading cause of male cancer-related deaths United States. MicroRNAs (miRNAs), an extensive class approximately 22 nucleotide noncoding RNAs, are often aberrantly expressed tissues fluids from prostate patients, but mechanisms how specific miRNAs regulate tumorigenesis metastasis poorly understood. Here, miR-888 was identified as a novel factor that promotes proliferation migration. resides within genomic cluster miRNA genes...