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

Garvanska, Dimitriya H. (författare)
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Alvarado, R. Elias (författare)
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
Mundt, Filip Oskar (författare)
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Lindquist, Richard, 1985- (författare)
Umeå universitet,Institutionen för klinisk mikrobiologi
Duel, Josephine Kerzel (författare)
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Coscia, Fabian (författare)
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Nilsson, Emma (författare)
Umeå universitet,Institutionen för klinisk mikrobiologi
Lokugamage, Kumari (författare)
Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
Johnson, Bryan A. (författare)
Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
Plante, Jessica A. (författare)
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
Morris, Dorothea R. (författare)
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
Vu, Michelle N. (författare)
Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
Estes, Leah K. (författare)
Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
McLeland, Alyssa M. (författare)
Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
Walker, Jordyn (författare)
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
Crocquet-Valdes, Patricia A. (författare)
Department of Pathology, University of Texas Medical Branch, TX, Galveston, United States
Mendez, Blanca Lopez (författare)
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Plante, Kenneth S. (författare)
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
Walker, David H. (författare)
Department of Pathology, University of Texas Medical Branch, TX, Galveston, United States
Weisser, Melanie Bianca (författare)
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Överby, Anna K. (författare)
Umeå universitet,Institutionen för klinisk mikrobiologi
Mann, Matthias (författare)
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Menachery, Vineet D. (författare)
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
Nilsson, Jakob (författare)
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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 (creator_code:org_t)
Springer Nature, 2024
2024
Engelska.
Ingår i: EMBO Reports. - : Springer Nature. - 1469-221X .- 1469-3178. ; 25:2, s. 902-926
Relaterad länk:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)
NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

Fragile X Syndrome
NSP3
SARS-CoV-2
Stress Granules
UBAP2L

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