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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Anthrolysin O and other gram-positive cytolysins are Toll-like receptor 4 agonists
TL;DR: Recombinant ALO can activate TLR4 in a manner independent of LPS contamination and, together with LT, can induce macrophage apoptosis and genetic evidence that ALO is required for induction of macrophages apoptosis in response to infection with live B. anthracis is provided.
Journal ArticleDOI
Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis.
Sandra Hanks,Sarah Adams,Jenny Douglas,Laura Arbour,David J. Atherton,Sevim Balci,Harald Bode,Mary E. Campbell,Murray Feingold,Gökhan Keser,Wim J. Kleijer,Grazia M.S. Mancini,John A. McGrath,Francesco Muntoni,Arti Nanda,M. Dawn Teare,Matthew L. Warman,F. Michael Pope,Andrea Superti-Furga,P. Andrew Futreal,Nazneen Rahman +20 more
TL;DR: It is demonstrated that JHF and ISH are allelic conditions and perturbation of basement-membrane matrix assembly as the cause of the characteristic perivascular hyaline deposition seen in these conditions.
Journal ArticleDOI
Anthrax: A disease of biowarfare and public health importance
TL;DR: The history, biology, life cycle, pathogenicity, virulence, epidemiology and potential of B. anthracis as biological weapon are described.
Patent
Modified transferrin fusion proteins
TL;DR: In this article, modified fusion proteins of transferrin and therapeutic proteins or peptides including soluble toxin receptors with increased serum half-life or serum stability are disclosed, and the preferred fusion proteins include those modified so that the transferrin moiety exhibits no or reduced glycosylation, binding to iron and/or binding to the receptor.
Journal ArticleDOI
The lethal and edema factors of anthrax toxin bind only to oligomeric forms of the protective antigen
TL;DR: EF and LF bind stably only to PA63 dimers or higher order oligomers, relevant to the kinetics and pathways of assembly of anthrax toxin complexes.
References
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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.
Journal ArticleDOI
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.