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Protein Interaction Mapping Identifies RBBP6 as a Negative Regulator of Ebola Virus Replication.
Batra, Jyoti; Hultquist, Judd F; Liu, Dandan; Shtanko, Olena; Von Dollen, John; Satkamp, Laura; Jang, Gwendolyn M; Luthra, Priya; Schwarz, Toni M; Small, Gabriel I; Arnett, Eusondia; Anantpadma, Manu; Reyes, Ann; Leung, Daisy W; Kaake, Robyn; Haas, Paige; Schmidt, Carson B; Schlesinger, Larry S; LaCount, Douglas J; Davey, Robert A; Amarasinghe, Gaya K; Basler, Christopher F; Krogan, Nevan J.
Afiliação
  • Batra J; Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Hultquist JF; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA; Division o
  • Liu D; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63105, USA.
  • Shtanko O; Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
  • Von Dollen J; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Satkamp L; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Jang GM; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Luthra P; Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
  • Schwarz TM; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Small GI; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63105, USA.
  • Arnett E; Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
  • Anantpadma M; Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
  • Reyes A; Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
  • Leung DW; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63105, USA.
  • Kaake R; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Haas P; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Schmidt CB; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
  • Schlesinger LS; Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
  • LaCount DJ; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
  • Davey RA; Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX 78245, USA.
  • Amarasinghe GK; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63105, USA.
  • Basler CF; Center for Microbial Pathogenesis, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. Electronic address: cbasler@gsu.edu.
  • Krogan NJ; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA. Electronic
Cell ; 175(7): 1917-1930.e13, 2018 12 13.
Article em En | MEDLINE | ID: mdl-30550789
ABSTRACT
Ebola virus (EBOV) infection often results in fatal illness in humans, yet little is known about how EBOV usurps host pathways during infection. To address this, we used affinity tag-purification mass spectrometry (AP-MS) to generate an EBOV-host protein-protein interaction (PPI) map. We uncovered 194 high-confidence EBOV-human PPIs, including one between the viral transcription regulator VP30 and the host ubiquitin ligase RBBP6. Domain mapping identified a 23 amino acid region within RBBP6 that binds to VP30. A crystal structure of the VP30-RBBP6 peptide complex revealed that RBBP6 mimics the viral nucleoprotein (NP) binding to the same interface of VP30. Knockdown of endogenous RBBP6 stimulated viral transcription and increased EBOV replication, whereas overexpression of either RBBP6 or the peptide strongly inhibited both. These results demonstrate the therapeutic potential of biologics that target this interface and identify additional PPIs that may be leveraged for novel therapeutic strategies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas Virais / Replicação Viral / Proteínas de Transporte / Doença pelo Vírus Ebola / Proteínas de Ligação a DNA / Ebolavirus Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas Virais / Replicação Viral / Proteínas de Transporte / Doença pelo Vírus Ebola / Proteínas de Ligação a DNA / Ebolavirus Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos