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The NSP3 protein of...
The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions
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- Garvanska, Dimitriya H. (author)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Alvarado, R. Elias (author)
- 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
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- Mundt, Filip Oskar (author)
- 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- (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Duel, Josephine Kerzel (author)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Coscia, Fabian (author)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Nilsson, Emma (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Lokugamage, Kumari (author)
- Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
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- Johnson, Bryan A. (author)
- Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
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- Plante, Jessica A. (author)
- 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
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- Morris, Dorothea R. (author)
- 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
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- Vu, Michelle N. (author)
- Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
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- Estes, Leah K. (author)
- Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
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- McLeland, Alyssa M. (author)
- Department of Microbiology and Immunology, University of Texas Medical Branch, TX, Galveston, United States
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- Walker, Jordyn (author)
- 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
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- Crocquet-Valdes, Patricia A. (author)
- Department of Pathology, University of Texas Medical Branch, TX, Galveston, United States
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- Mendez, Blanca Lopez (author)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Plante, Kenneth S. (author)
- 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
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- Walker, David H. (author)
- Department of Pathology, University of Texas Medical Branch, TX, Galveston, United States
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- Weisser, Melanie Bianca (author)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Överby, Anna K. (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Mann, Matthias (author)
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Menachery, Vineet D. (author)
- 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
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- Nilsson, Jakob (author)
- 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
- English.
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In: EMBO Reports. - : Springer Nature. - 1469-221X .- 1469-3178. ; 25:2, s. 902-926
- Related links:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- 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)
Keyword
- Fragile X Syndrome
- NSP3
- SARS-CoV-2
- Stress Granules
- UBAP2L
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Garvanska, Dimit ...
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Alvarado, R. Eli ...
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Mundt, Filip Osk ...
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Lindquist, Richa ...
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Duel, Josephine ...
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Coscia, Fabian
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show more...
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Nilsson, Emma
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Lokugamage, Kuma ...
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Johnson, Bryan A ...
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Plante, Jessica ...
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Morris, Dorothea ...
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Vu, Michelle N.
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Estes, Leah K.
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McLeland, Alyssa ...
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Walker, Jordyn
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Crocquet-Valdes, ...
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Mendez, Blanca L ...
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Plante, Kenneth ...
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Walker, David H.
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Weisser, Melanie ...
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Överby, Anna K.
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Mann, Matthias
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Menachery, Vinee ...
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Nilsson, Jakob
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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EMBO Reports
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Umeå University