Journal ArticleDOI
Identification of the cellular receptor for anthrax toxin.
Kenneth A. Bradley,Jeremy Mogridge,Jeremy Mogridge,Michael Mourez,Robert J. Collier,John A. Young +5 more
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TLDR
The cloning of the human PA receptor is described using a genetic complementation approach and a soluble version of this domain can protect cells from the action of the toxin.Abstract:
The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages. Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.read more
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Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1.
Jia Hong,Robert C. Doebele,Mark W. Lingen,Lawrence A. Quilliam,Wei-Jen Tang,Marsha Rich Rosner +5 more
TL;DR: Epac and Rap1 are identified as key regulators of signaling cascades leading to endothelial cell chemotaxis in human endothelial cells.
Journal ArticleDOI
Ratcheting up protein translocation with anthrax toxin
TL;DR: It is suggested a cyclical thermodynamic order‐to‐disorder mechanism (akin to a heat‐engine cycle) is central to underlying protein translocation: peptide substrates nonspecifically bind to molecular clamps, which possess adjustable affinities; polypeptides compress into helical structures; these clamps undergo proton‐gated switching; and the substrate subsequently expands regaining its unfolded state conformational entropy upon translocation.
Journal ArticleDOI
Protective immunity evoked against anthrax lethal toxin after a single intramuscular administration of an adenovirus-based vaccine encoding humanized protective antigen.
TL;DR: With a single intramuscular administration to mice of 10(9) particle units of AdsechPA, a dose that can be scaled to human use, anti-PA antibodies were evoked more rapidly and at a higher level than with a single administration of the new U.S. military recombinant PA/Alhydrogel vaccine.
Journal ArticleDOI
Three-dimensional Model of the Pore Form of Anthrax Protective Antigen. Structure and Biological Implications
TL;DR: The PA63 pore was modeled using the X-ray structures of monomeric PA and heptameric α-hemolysin as templates to afford new insights into the binding mode of PA on the membrane surface, the prepore-pore transition, and the mechanism of cell entry by anthrax toxin.
Journal ArticleDOI
Purified Bacillus anthracis lethal toxin complex formed in vitro and during infection exhibits functional and biological activity.
Rekha G. Panchal,Kelly M. Halverson,Wilson J. Ribot,Douglas Lane,Tara Kenny,Teresa G. Abshire,John W. Ezzell,Timothy A. Hoover,Bradford S. Powell,Stephen F. Little,John J. Kasianowicz,Sina Bavari +11 more
TL;DR: It is found that purified (PA63)7-LF complex exhibited biological and functional activities similar to the free LF and was able to cleave both a synthetic peptide substrate and endogenous mitogen-activated protein kinase kinase substrates and kill susceptible macrophage cells.
References
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Journal ArticleDOI
Genes expressed in human tumor endothelium
Brad St. Croix,Carlo Rago,Carlo Rago,Victor E. Velculescu,Giovanni Traverso,Katharine E. Romans,Elizabeth A. Montgomery,Anita Lal,Gregory J. Riggins,Christoph Lengauer,Bert Vogelstein,Bert Vogelstein,Kenneth W. Kinzler +12 more
TL;DR: It is demonstrated that tumor and normal endothelium are distinct at the molecular level, a finding that may have significant implications for the development of anti-angiogenic therapies.
Journal ArticleDOI
Clonal selection and learning in the antibody system
TL;DR: A second selection process occurs during immune responses in which a new antibody repertoire is generated through somatic hypermutation, where only mutants binding antigen with high affinity survive to become memory cells.
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Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells
TL;DR: The ability to concentrate vesicular stomatitis virus G glycoprotein pseudotyped vectors will facilitate gene therapy model studies and other gene transfer experiments that require direct delivery of vectors in vivo, and facilitate genetic studies in nonmammalian species, including the important zebrafish developmental system.
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Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization.
TL;DR: The successful isolation of these prepuberal cell types was accomplished by defining distinctive morphological characteristics of the cells and assessing the identity and purity of the isolated cell types by microscopy.