A Mutational Analysis of Residues in Cholera Toxin A1 Necessary for Interaction with Its Substrate, the Stimulatory G Protein Gsα
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Hras Intracellular Trafficking and Signal Transduction Jodi Ho-Jung Mckay Iowa State University
Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2007 HRas intracellular trafficking and signal transduction Jodi Ho-Jung McKay Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Biological Phenomena, Cell Phenomena, and Immunity Commons, Cancer Biology Commons, Cell Biology Commons, Genetics and Genomics Commons, and the Medical Cell Biology Commons Recommended Citation McKay, Jodi Ho-Jung, "HRas intracellular trafficking and signal transduction" (2007). Retrospective Theses and Dissertations. 13946. https://lib.dr.iastate.edu/rtd/13946 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. HRas intracellular trafficking and signal transduction by Jodi Ho-Jung McKay A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Genetics Program of Study Committee: Janice E. Buss, Co-major Professor Linda Ambrosio, Co-major Professor Diane Bassham Drena Dobbs Ted Huiatt Iowa State University Ames, Iowa 2007 Copyright © Jodi Ho-Jung McKay, 2007. All rights reserved. UMI Number: 3274881 Copyright 2007 by McKay, Jodi Ho-Jung All rights reserved. UMI Microform 3274881 Copyright 2008 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. -
ADP-Ribosylation Factor, a Small GTP-Binding Protein, Is Required for Binding of the Coatomer Protein Fl-COP to Golgi Membranes JULIE G
Proc. Natl. Acad. Sci. USA Vol. 89, pp. 6408-6412, July 1992 Biochemistry ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein fl-COP to Golgi membranes JULIE G. DONALDSON*, DAN CASSEL*t, RICHARD A. KAHN*, AND RICHARD D. KLAUSNER* *Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, and tLaboratory of Biological Chemistry, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Communicated by Marc Kirschner, April 20, 1992 (receivedfor review February 11, 1992) ABSTRACT The coatomer is a cytosolic protein complex localized to the Golgi complex, although their functions have that reversibly associates with Golgi membranes and is Impli- not been defined. Distinct among these proteins is the ADP- cated in modulating Golgi membrane transport. The associa- ribosylation factor (ARF), originally identified as a cofactor tion of 13-COP, a component of coatomer, with Golgi mem- required for in vitro cholera toxin-catalyzed ADP- branes is enhanced by guanosine 5'-[v-thioltriphosphate ribosylation of the a subunit of the trimeric GTP-binding (GTP[yS]), a nonhydrolyzable analogue of GTP, and by a protein G, (G,.) (19). ARF is an abundant cytosolic protein mixture of aluminum and fluoride ions (Al/F). Here we show that reversibly associates with Golgi membranes (20, 21). that the ADP-ribosylation factor (ARF) is required for the ARF has been shown to be present on Golgi coated vesicles binding of (-COP. Thus, 13-COP contained in a coatomer generated in the presence of GTP[yS], but it is not a com- fraction that has been resolved from ARF does not bind to Golgi ponent of the cytosolic coatomer (22). -
Crystal Structure of a New Heat-Labile Enterotoxin, LT-Iib
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Research Article 665 Crystal structure of a new heat-labile enterotoxin, LT-IIb Focco van den Akker1, Steve Sarfaty1,2, Edda M Twiddy3, Terry D Connell3†, Randall K Holmes3‡ and Wim GJ Hol1,2* Background: Cholera toxin from Vibrio cholerae and the type I heat-labile Addresses: 1Departments of Biological Structure enterotoxins (LT-Is) from Escherichia coli are oligomeric proteins with AB and Biochemistry & Biomolecular Structure 5 Center, University of Washington, 2Howard structures. The type II heat-labile enterotoxins (LT-IIs) from E. coli are structurally Hughes Medical Institute, University of similar to, but antigenically distinct from, the type I enterotoxins. The A subunits Washington, Box 357742, Seattle, WA 98195, of type I and type II enterotoxins are homologous and activate adenylate cyclase USA and 3Department of Microbiology and Immunology, Uniformed Services University of the by ADP-ribosylation of a G protein subunit, Gsa. However, the B subunits of type I and type II enterotoxins differ dramatically in amino acid sequence and Health Sciences, Bethesda, MD 20814, USA. ganglioside-binding specificity. The structure of LT-IIb was determined both as a Present addresses: †Department of Microbiology, prototype for other LT-IIs and to provide additional insights into School of Medicine and Biomedical Sciences, structure/function relationships among members of the heat-labile enterotoxin Buffalo, NY 14214-3078, USA and ‡Department family and the superfamily of ADP-ribosylating protein toxins. of Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. -
Identification of Motifs in Cholera Toxin A1 Polypeptide That Are Required for Its Interaction with Human ADP-Ribosylation Factor 6 in a Bacterial Two-Hybrid System
Identification of motifs in cholera toxin A1 polypeptide that are required for its interaction with human ADP-ribosylation factor 6 in a bacterial two-hybrid system Michael G. Jobling and Randall K. Holmes* Department of Microbiology, University of Colorado Health Sciences Center, Denver, CO 80220 Edited by John J. Mekalanos, Harvard Medical School, Boston, MA, and approved October 20, 2000 (received for review September 14, 2000) The latent ADP-ribosyltransferase activity of cholera toxin (CT) that teins called ADP-ribosylation factors (ARFs; refs. 5 and 6). is activated after proteolytic nicking and reduction is associated ARFs are members of a highly conserved multigene family of with the CT A1 subunit (CTA1) polypeptide. This activity is stimu- small GTP-binding proteins, originally identified as activators of lated in vitro by interaction with eukaryotic proteins termed CT. They interact with several other proteins and are ubiqui- ADP-ribosylation factors (ARFs). We analyzed this interaction in a tously involved in membrane trafficking events (7). ARFs must modified bacterial two-hybrid system in which the T18 and T25 be in the GTP-bound form to be active. There are six mammalian fragments of the catalytic domain of Bordetella pertussis adenylate ARFs (five human) that fall into three classes: ARFs 1, 2, and cyclase were fused to CTA1 and human ARF6 polypeptides, respec- 3 (class I), ARFs 4 and 5 (class II), and ARF6 (class III). Class tively. Direct interaction between the CTA1 and ARF6 domains in I ARFs regulate the assembly of several types of vesicle coat these hybrid proteins reconstituted the adenylate cyclase activity complexes (8). -
Instability of Toxin a Subunit of AB5 Toxins in the Bacterial Periplasm Caused by Deficiency of Their Cognate B Subunits
Biochimica et Biophysica Acta 1808 (2011) 2359–2365 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamem Instability of toxin A subunit of AB5 toxins in the bacterial periplasm caused by deficiency of their cognate B subunits Sang-Hyun Kim a, Su Hyang Ryu a, Sang-Ho Lee a, Yong-Hoon Lee a, Sang-Rae Lee a, Jae-Won Huh a, Sun-Uk Kim a, Ekyune Kim d, Sunghyun Kim b, Sangyong Jon b, Russell E. Bishop c,⁎, Kyu-Tae Chang a,⁎⁎ a The National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongwon, Chungbuk 363–883, Republic of Korea b School of Life Science, Gwangju Institute of Science and Technology (GIST), 1 Oryong-dong, Gwangju 500–712, Republic of Korea c Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 d College of Pharmacy, Catholic University of Daegu, Hayang-eup, Gyeongsan, Gyeongbuk 712-702, Republic of Korea article info abstract Article history: Shiga toxin (STx) belongs to the AB5 toxin family and is transiently localized in the periplasm before secretion Received 26 April 2011 into the extracellular milieu. While producing outer membrane vesicles (OMVs) containing only A subunit of Received in revised form 3 June 2011 the toxin (STxA), we created specific STx1B- and STx2B-deficient mutants of E. coli O157:H7. Surprisingly, Accepted 23 June 2011 STxA subunit was absent in the OMVs and periplasm of the STxB-deficient mutants. In parallel, the A subunit Available online 5 July 2011 of heat-labile toxin (LT) of enterotoxigenic E. -
Supplementary Table 2
Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942 -
Cellular Activity of Salmonella Typhimurium Artab Toxin and Its Receptor-Binding Subunit
toxins Article Cellular Activity of Salmonella Typhimurium ArtAB Toxin and Its Receptor-Binding Subunit Elise Overgaard 1, Brad Morris 2, Omid Mohammad Mousa 2 , Emily Price 3, Adriana Rodriguez 2, Leyla Cufurovic 2, Richard S. Beard 4 and Juliette K. Tinker 1,2,* 1 Biomolecular Sciences Graduate Program, Boise State University, Boise, ID 83725, USA; [email protected] 2 Department of Biology, Boise State University, Boise, ID 83725, USA; [email protected] (B.M.); [email protected] (O.M.M.); [email protected] (A.R.); [email protected] (L.C.) 3 Idaho Veterans Research and Education Foundation, Infectious Diseases Section, Boise, ID 83702, USA; [email protected] 4 Biomolecular Research Center, Boise State University, Boise, ID 83725, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-208-426-5472 Abstract: Salmonellosis is among the most reported foodborne illnesses in the United States. The Salmonella enterica Typhimurium DT104 phage type, which is associated with multidrug-resistant disease in humans and animals, possesses an ADP-ribosylating toxin called ArtAB. Full-length artAB has been found on a number of broad-host-range non-typhoidal Salmonella species and serovars. ArtAB is also homologous to many AB5 toxins from diverse Gram-negative pathogens, including cholera toxin (CT) and pertussis toxin (PT), and may be involved in Salmonella pathogenesis, however, in vitro cellular toxicity of ArtAB has not been characterized. artAB was cloned into E. coli and initially isolated using a histidine tag (ArtABHIS) and nickel chromatography. ArtABHIS was found to bind to African green monkey kidney epithelial (Vero) cells using confocal microscopy and to Citation: Overgaard, E.; Morris, B.; interact with glycans present on fetuin and monosialotetrahexosylganglioside (GM1) using ELISA. -
Virtuous Aspects of Vicious Bacterial Toxins
Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2015, 7(6):279-289 ISSN : 0975-7384 Review Article CODEN(USA) : JCPRC5 Virtuous aspects of vicious bacterial toxins Pankaj Gautam, Pranjali Gupta, Promila Sharma and Pranshu Dangwal Department of Biotechnology, Graphic Era University, 566/6, Bell Road, Clement Town, Dehradun, Uttarakhand(India) _____________________________________________________________________________________________ ABSTRACT Pathogenic bacteria exert their harmful effects in host through a cascade of virulence factors: exotoxins, endotoxin, invasions proteins and the like. Various toxins secreted by different bacteria not only subvert the host intracellular signaling pathways but also have unique affinity for specific host cells. Detailed information has been accumulated over the years regarding the purification, chemical characterization, enzymic action and architecture of various bacterial toxins. Toxins ability to bind to the specific target cells makes them good candidate for drug delivery and in cancer therapeutics. A number of immunotoxins; hybrid molecules of bacterial toxins and antibodies, have wide applications in cancer and are currently under clinical trial. Advances in genomics and proteomics have created a wealth of information related to the nucleotide and protein sequences of numerous toxins and different databases (DBETH, VFDB, BETAWRAP, RASTA) are available with elaborate information thereof. In present review we have provided a brief account of therapeutic aspect of bacterial toxins and an effort has been made to facilitate the reader’s understanding as to how we can turn the vicious toxin into virtuous toxin for human benefits. Key words: .Bacterial Toxin, Immunotoxins, AB 5, A2B5, Toxin databases, Therapeutic toxin. _____________________________________________________________________________________________ Bacterial toxins; the soluble antigens, secreted by a number of pathogenic bacteria has a standing reputation of being a poison secreted during the course of pathogenesis. -
Lysophosphatidic Acid Activates Arf6 to Promote the Mesenchymal Malignancy of Renal Cancer
ARTICLE Received 6 Jun 2015 | Accepted 6 Jan 2016 | Published 8 Feb 2016 DOI: 10.1038/ncomms10656 OPEN Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer Shigeru Hashimoto1,*, Shuji Mikami2,*,w, Hirokazu Sugino1, Ayumu Yoshikawa1, Ari Hashimoto1, Yasuhito Onodera1, Shotaro Furukawa1,3, Haruka Handa1, Tsukasa Oikawa1, Yasunori Okada4, Mototsugu Oya5 & Hisataka Sabe1 Acquisition of mesenchymal properties by cancer cells is critical for their malignant behaviour, but regulators of the mesenchymal molecular machinery and how it is activated remain elusive. Here we show that clear cell renal cell carcinomas (ccRCCs) frequently utilize the Arf6-based mesenchymal pathway to promote invasion and metastasis, similar to breast cancers. In breast cancer cells, ligand-activated receptor tyrosine kinases employ GEP100 to activate Arf6, which then recruits AMAP1; and AMAP1 then binds to the mesenchymal- specific protein EPB41L5, which promotes epithelial–mesenchymal transition and focal adhesion dynamics. In renal cancer cells, lysophosphatidic acid (LPA) activates Arf6 via its G-protein-coupled receptors, in which GTP-Ga12 binds to EFA6. The Arf6-based pathway may also contribute to drug resistance. Our results identify a specific mesenchymal molecular machinery of primary ccRCCs, which is triggered by a product of autotaxin and it is associated with poor outcome of patients. 1 Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. 2 Division of Diagnostic Pathology, Keio University Hospital, Tokyo 160-0016, Japan. 3 Department of Gastroenterological Surgery II, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. 4 Department of Pathology, Keio University School of Medicine, Tokyo 160-0016, Japan. -
Chemical Strategies to Target Bacterial Virulence
Review pubs.acs.org/CR Chemical Strategies To Target Bacterial Virulence † ‡ ‡ † ‡ § ∥ Megan Garland, , Sebastian Loscher, and Matthew Bogyo*, , , , † ‡ § ∥ Cancer Biology Program, Department of Pathology, Department of Microbiology and Immunology, and Department of Chemical and Systems Biology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California 94305, United States ABSTRACT: Antibiotic resistance is a significant emerging health threat. Exacerbating this problem is the overprescription of antibiotics as well as a lack of development of new antibacterial agents. A paradigm shift toward the development of nonantibiotic agents that target the virulence factors of bacterial pathogens is one way to begin to address the issue of resistance. Of particular interest are compounds targeting bacterial AB toxins that have the potential to protect against toxin-induced pathology without harming healthy commensal microbial flora. Development of successful antitoxin agents would likely decrease the use of antibiotics, thereby reducing selective pressure that leads to antibiotic resistance mutations. In addition, antitoxin agents are not only promising for therapeutic applications, but also can be used as tools for the continued study of bacterial pathogenesis. In this review, we discuss the growing number of examples of chemical entities designed to target exotoxin virulence factors from important human bacterial pathogens. CONTENTS 3.5.1. C. diphtheriae: General Antitoxin Strat- egies 4435 1. Introduction 4423 3.6. Pseudomonas aeruginosa 4435 2. How Do Bacterial AB Toxins Work? 4424 3.6.1. P. aeruginosa: Inhibitors of ADP Ribosyl- 3. Small-Molecule Antivirulence Agents 4426 transferase Activity 4435 3.1. Clostridium difficile 4426 3.7. Bordetella pertussis 4436 3.1.1. C. -
Dysfunction Cytokine Release and Pancreatic Islet Graft Polypeptide-Induced Proinflammatory IL-1 Blockade Attenuates Islet Amylo
IL-1 Blockade Attenuates Islet Amyloid Polypeptide-Induced Proinflammatory Cytokine Release and Pancreatic Islet Graft Dysfunction This information is current as of September 23, 2021. Clara Westwell-Roper, Derek L. Dai, Galina Soukhatcheva, Kathryn J. Potter, Nico van Rooijen, Jan A. Ehses and C. Bruce Verchere J Immunol 2011; 187:2755-2765; Prepublished online 3 August 2011; Downloaded from doi: 10.4049/jimmunol.1002854 http://www.jimmunol.org/content/187/5/2755 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2011/08/04/jimmunol.100285 Material 4.DC1 References This article cites 57 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/187/5/2755.full#ref-list-1 Why The JI? Submit online. by guest on September 23, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology IL-1 Blockade Attenuates Islet Amyloid Polypeptide-Induced Proinflammatory Cytokine Release and Pancreatic Islet Graft Dysfunction Clara Westwell-Roper,* Derek L. -
Fast Structural Responses of Gap Junction Membrane Domains to AB5
Fast structural responses of gap junction membrane PNAS PLUS domains to AB5 toxins Irina V. Majoula,1, Liang Gaob, Eric Betzigb, Daria Onichtchoukc, Eugenia Butkevichd, Yuri Kozlove, Feliksas Bukauskasf, Michael V. L. Bennettf, Jennifer Lippincott-Schwartzg,1, and Rainer Dudena,1 aInstitute of Biology, Center for Structural and Cell Biology in Medicine, University of Lübeck, 23562 Lübeck, Germany; bJanelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147; cCenter for Biological Signaling Studies, Albert Ludwigs University, 79104 Freiburg, Germany; dDrittes Physikalisches Institut, Biophysik, Georg-August-Universität, 37077 Göttingen, Germany; eV.A. Engelhardt Institute for Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; fDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461; and gEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 Contributed by Jennifer Lippincott-Schwartz, September 9, 2013 (sent for review June 20, 2013) Gap junctions (GJs) represent connexin-rich membrane domains 1 (STx1), or Shiga toxin type 2 (STx2, also known as Vero-toxin that connect interiors of adjoining cells in mammalian tissues. How and released by EHEC bacteria), according to protocols we have fast GJs can respond to bacterial pathogens has not been known described previously (16–18). CTX and STx1 both consist of previously. Using Bessel beam plane illumination and confocal a homopentameric B-subunit and a catalytic A-subunit (for spinning disk microscopy, we found fast (∼500 ms) formation of a schematic structure see Fig. 1C). The five identical B-subunits connexin-depleted regions (CDRs) inside GJ plaques between cells are responsible for binding to the plasma membrane via specific exposed to AB5 toxins.