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  • Garvanska, Dimitriya H.Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (author)

The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions

  • Article/chapterEnglish2024

Publisher, publication year, extent ...

  • Springer Nature,2024
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-221660
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-221660URI
  • https://doi.org/10.1038/s44319-023-00043-zDOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Viruses interact with numerous host factors to facilitate viral replication and to dampen antiviral defense mechanisms. We currently have a limited mechanistic understanding of how SARS-CoV-2 binds host factors and the functional role of these interactions. Here, we uncover a novel interaction between the viral NSP3 protein and the fragile X mental retardation proteins (FMRPs: FMR1, FXR1-2). SARS-CoV-2 NSP3 mutant viruses preventing FMRP binding have attenuated replication in vitro and reduced levels of viral antigen in lungs during the early stages of infection. We show that a unique peptide motif in NSP3 binds directly to the two central KH domains of FMRPs and that this interaction is disrupted by the I304N mutation found in a patient with fragile X syndrome. NSP3 binding to FMRPs disrupts their interaction with the stress granule component UBAP2L through direct competition with a peptide motif in UBAP2L to prevent FMRP incorporation into stress granules. Collectively, our results provide novel insight into how SARS-CoV-2 hijacks host cell proteins and provides molecular insight into the possible underlying molecular defects in fragile X syndrome.

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  • Alvarado, R. EliasDepartment of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States; Institute for Translational Sciences, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Mundt, Filip OskarNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (author)
  • Lindquist, Richard,1985-Umeå universitet,Institutionen för klinisk mikrobiologi(Swepub:umu)rili0007 (author)
  • Duel, Josephine KerzelNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (author)
  • Coscia, FabianNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (author)
  • Nilsson, EmmaUmeå universitet,Institutionen för klinisk mikrobiologi(Swepub:umu)niem6001 (author)
  • Lokugamage, KumariDepartment of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Johnson, Bryan A.Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Plante, Jessica A.Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States; World Reference Center of Emerging Viruses and Arboviruses, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Morris, Dorothea R.Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States; Institute for Translational Sciences, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Vu, Michelle N.Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Estes, Leah K.Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States (author)
  • McLeland, Alyssa M.Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Walker, JordynDepartment of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States; World Reference Center of Emerging Viruses and Arboviruses, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Crocquet-Valdes, Patricia A.Department of Pathology, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Mendez, Blanca LopezNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (author)
  • Plante, Kenneth S.Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States; World Reference Center of Emerging Viruses and Arboviruses, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Walker, David H.Department of Pathology, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Weisser, Melanie BiancaNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (author)
  • Överby, Anna K.Umeå universitet,Institutionen för klinisk mikrobiologi(Swepub:umu)anaovy99 (author)
  • Mann, MatthiasNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (author)
  • Menachery, Vineet D.Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States; World Reference Center of Emerging Viruses and Arboviruses, University of Texas Medical Branch, TX, Galveston, United States (author)
  • Nilsson, JakobNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (author)
  • Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States; Institute for Translational Sciences, University of Texas Medical Branch, TX, Galveston, United States (creator_code:org_t)

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  • In:EMBO Reports: Springer Nature25:2, s. 902-9261469-221X1469-3178

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