A5054012693- Bacterial Infections and Vaccines
- Endoplasmic Reticulum Stress and Disease
- Bacterial Genetics and Biotechnology
- Glycogen Storage Diseases and Myoclonus
- Parkinson's Disease Mechanisms and Treatments
- Electron and X-Ray Spectroscopy Techniques
- Advanced Electron Microscopy Techniques and Applications
- Escherichia coli research studies
- Lysosomal Storage Disorders Research
- Microbial infections and disease research
- Autophagy in Disease and Therapy
- Biotin and Related Studies
- Vibrio bacteria research studies
- Cellular transport and secretion
- Genomics and Phylogenetic Studies
- Heme Oxygenase-1 and Carbon Monoxide
- Infective Endocarditis Diagnosis and Management
- Bacterial biofilms and quorum sensing
- Lipid Membrane Structure and Behavior
- Bacillus and Francisella bacterial research
- Cellular Mechanics and Interactions
- Biochemical Acid Research Studies
- Genetic Neurodegenerative Diseases
- Peptidase Inhibition and Analysis
- Protein Tyrosine Phosphatases
Purdue University West Lafayette
2016-2024
The Ohio State University
2024
Center for Cancer Research
2020
State Street (United States)
2018
University of California, San Diego
2005-2011
Howard Hughes Medical Institute
2007-2010
University of California, Los Angeles
1998-2008
University of Maryland, College Park
1994
ABSTRACT Adherence to ciliated respiratory epithelial cells is considered a critical early step in Bordetella pathogenesis. For pertussis , the etiologic agent of whooping cough, several factors have been shown mediate adherence and cell lines vitro. These putative adhesins include filamentous hemagglutinin (FHA), fimbriae, pertactin, toxin. Determining precise roles each these vivo, however, has difficult, due part lack natural-host animal models for use with B. . Using closely related...
Lafora disease (LD) is a progressive myoclonic epilepsy resulting in severe neurodegeneration followed by death. A hallmark of LD the accumulation insoluble polyglucosans called bodies (LBs). caused mutations gene encoding phosphatase laforin, which reportedly exists solely vertebrates. We utilized bioinformatics screen to identify laforin orthologues five protists. These protists evolved from progenitor red alga and synthesize an carbohydrate whose composition closely resembles LBs....
Bordetella species utilize the BvgAS (Bordetella virulence gene) two-component signal transduction system to sense environment and regulate gene expression among at least three phases: a virulent Bvg+ phase, nonvirulent Bvg- an intermediate Bvgi phase. Genes expressed in phase encode known factors, including adhesins such as filamentous hemagglutinin (FHA) fimbriae, well toxins bifunctional adenylate cyclase/hemolysin (ACY). Previous studies showed that FHA fimbriae continue be expressed,...
Summary Bordetella bronchiseptica utilizes a type III secretion system (TTSS) for induction of non‐apoptotic cytotoxicity in host cells and modulation immunity. The identity TTSS effectors, however, has remained elusive. Here we report genome‐wide screen effectors based on shared biophysical functional characteristics class I chaperones their frequent colocalization with effectors. When applied to B. , the identified first chaperone‐effector locus, btcA‐bteA experimentally confirmed its...
A new family of adenylyltransferases, defined by the presence a Fic domain, was recently discovered to catalyze addition adenosine monophosphate (AMP) Rho GTPases (Yarbrough, M. L., Li, Y., Kinch, L. N., Grishin, N. V., Ball, H. and Orth, K. (2009) Science 323, 269-272; Worby, C. A., Mattoo, S., Kruger, R. P., Corbeil, B., Koller, Mendez, J. C., Zekarias, Lazar, Dixon, E. Mol. Cell 34, 93-103). This adenylylation event inactivates preventing them from binding their downstream effectors. We...
Lipid membranes are involved in regulating biochemical and biological processes modulating the selective permeability of cells, organelles, vesicles. Membrane composition, charge, curvature, fluidity all have concerted effects on cellular signaling homeostasis. The ability to prepare artificial lipid assemblies that mimic has enabled investigators obtain considerable insight into biomolecule-membrane interactions. nanoscale can vary greatly size composition consist a single monolayer,...
ABSTRACT Fimbriae are filamentous, cell surface structures which have been proposed to mediate attachment of Bordetella species respiratory epithelium. bronchiseptica has four known fimbrial genes: fim2 , fim3 fimX and fimA . While these genes unlinked on the chromosome, their protein products assembled secreted by a single apparatus encoded fimBCD locus. The locus is embedded within fha operon, whose encode another putative adhesin, filamentous hemagglutinin (FHA). We constructed Fim − B....
Summary The BvgAS virulence control system regulates the expression of type III secretion genes in Bordetella subspecies that infect humans and other mammals. We have identified five open reading frames, btrS , btrU btrX btrW btrV are activated by encode regulatory factors at levels transcription, protein secretion. gene product bears sequence similarity to ECF ( e xtra c ytoplasmic f unction) sigma is required for transcription bsc locus. proteins predicted contain PP2C‐like Ser...
ABSTRACT Newly recognized Fic family virulence proteins may be important in many bacterial pathogens. To relate cellular mechanisms to pathogenesis and immune protection, we studied the cytotoxicity of Histophilus somni immunoglobulin-binding protein A (IbpA) direct repeat 2 domain (DR2/Fic) for natural host target cells. Live virulent IbpA-producing H. strain 2336, a cell-free culture supernatant (CCS) this strain, or recombinant DR2/Fic (rDR2/Fic) caused dramatic retraction rounding bovine...
Type III secretion system (T3SS) tip complexes serve as adaptors that bridge the T3SS needle and pore-forming translocation apparatus. In this report we demonstrate Bsp22, most abundantly secreted substrate of Bordetella T3SS, self-polymerizes to form bronchiseptica complex. Bsp22 is required for both T3SS-mediated cytotoxicity against eukaryotic cells haemoglobin release from erythrocytes. Bacterial two-hybrid analysis protein pull-down assays demonstrated ability associate with itself bind...
ABSTRACT We describe a method, termed cryoAPEX, which couples chemical fixation and high-pressure freezing of cells with peroxidase tagging (APEX) to allow precise localization membrane proteins in the context well-preserved subcellular architecture. Further, cryoAPEX is compatible electron tomography. As an example, we apply obtain high-resolution three-dimensional contextual map human FIC (filamentation induced by cAMP) protein, HYPE (also known as FICD). single-pass protein that localizes...
ABSTRACT We have recently described a multicomponent cascade that regulates type III secretion in Bordetella . This includes group of proteins, BtrU, BtrW, and BtrV, contain an array domains define partner-switching complexes previously characterized gram-positive bacteria. BtrU contains PP2C-like serine phosphatase domain, BtrW kinase/anti-sigma factor motif, BtrV anti-sigma antagonist domain. On the basis genetic studies sequence similarity with RsbU-RsbW-RsbV SpoIIE-SpoIIAB-SpoIIAA...
The 2nd International Symposium on the Chaperone Code took place October 26-28, 2023 at Hilton Alexandria Old Town, VA, USA. event featured more than 100 attendees from ten countries and provided a dynamic platform for established researchers, emerging investigators, postdoctoral fellows, students to share insights ideas diverse facets of molecular chaperones with strong focus their regulation by post-translational modifications. format fostered discussions collaboration among participants....
Adenosyl monophosphate (AMP)ylation (the covalent transfer of an AMP from Adenosine Triphosphate (ATP) onto a target protein) is catalyzed by the human enzyme Huntingtin Yeast Interacting Partner E (HYPE)/FicD to regulate its substrate, heat shock chaperone binding immunoglobulin protein (BiP). HYPE-mediated AMPylation BiP critical for maintaining proteostasis in endoplasmic reticulum and mounting unfolded response times proteostatic imbalance. Thus, manipulating HYPE's enzymatic activity...
Fic (filamentation induced by cAMP) proteins regulate diverse cell signaling events post-translationally modifying their protein targets, predominantly the addition of an AMP (adenosine monophosphate). This modification is called Fic-mediated adenylylation or AMPylation. We previously reported that human protein, HYPE/FicD, a novel regulator unfolded response (UPR) maintains homeostasis in endoplasmic reticulum (ER) to stress from misfolded proteins. Specifically, HYPE regulates UPR...
3-Carboxy-cis,cis-muconate lactonizing enzyme (CMLE; EC 5.5.1.5) from Neurospora crassa catalyzes the reversible gamma-lactonization of 3-carboxy-cis,cis-muconate by a syn-1,2 addition-elimination reaction. The stereochemical and regiochemical course reaction is (i) opposite that CMLE Pseudomonas putida (EC 5.5.1.2) (ii) identical to cis,cis-muconate (MLE; 5.5.1.1) P. putida. In order determine mechanistic evolutionary relationships between N. procaryotic cycloisomerases, we have purified...