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| Item Type: | Article |
|---|---|
| Title: | The NSP3 protein of SARS-CoV-2 binds fragile X mental retardation proteins to disrupt UBAP2L interactions |
| Creators Name: | Garvanska, D.H., Alvarado, R.E., Mundt, F.O., Lindqvist, R., Duel, J.K., Coscia, F., Nilsson, E., Lokugamage, K., Johnson, B.A., Plante, J.A., Morris, D.R., Vu, M.N., Estes, L.K., McLeland, A.M., Walker, J., Crocquet-Valdes, P.A., Mendez, B.L., Plante, K.S., Walker, D.H., Weisser, M.B., Överby, A.K., Mann, M., Menachery, V.D. and Nilsson, J. |
| Abstract: | 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. |
| Keywords: | SARS-CoV-2, Fragile X Syndrome, UBAP2L, Stress Granules, NSP3 |
| Source: | EMBO Reports |
| ISSN: | 1469-221X |
| Publisher: | EMBO Press |
| Volume: | 25 |
| Number: | 2 |
| Page Range: | 902-926 |
| Date: | 13 February 2024 |
| Official Publication: | https://doi.org/10.1038/s44319-023-00043-z |
| PubMed: | View item in PubMed |
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