8th1
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G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP1-N interaction in the context of viral infection remain unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively and reciprocally disrupt their interaction. We found that mutation of F17 within the N protein led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation resulted in a significant decrease in viral replication and pathogenesis in vivo, indicating that the G3BP1-N interaction promotes infection by suppressing the ability of G3BP1 to form stress granules. | G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP1-N interaction in the context of viral infection remain unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively and reciprocally disrupt their interaction. We found that mutation of F17 within the N protein led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation resulted in a significant decrease in viral replication and pathogenesis in vivo, indicating that the G3BP1-N interaction promotes infection by suppressing the ability of G3BP1 to form stress granules. | ||
| - | Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication.,Yang Z, Johnson BA, Meliopoulos VA, Ju X, Zhang P, Hughes MP, Wu J, Koreski KP, Chang TC, Wu G, Hixon J, Duffner J, Wong K, Lemieux R, Lokugamage KG, Alvardo RE, Crocquet-Valdes PA, Walker DH, Plante KS, Plante JA, Weaver SC, Kim HJ, Meyers R, Schultz-Cherry S, Ding Q, Menachery VD, Taylor JP bioRxiv. 2023 Jun 30:2023.06.29.546885. doi: 10.1101/2023.06.29.546885 | + | Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication.,Yang Z, Johnson BA, Meliopoulos VA, Ju X, Zhang P, Hughes MP, Wu J, Koreski KP, Chang TC, Wu G, Hixon J, Duffner J, Wong K, Lemieux R, Lokugamage KG, Alvardo RE, Crocquet-Valdes PA, Walker DH, Plante KS, Plante JA, Weaver SC, Kim HJ, Meyers R, Schultz-Cherry S, Ding Q, Menachery VD, Taylor JP bioRxiv [Preprint]. 2023 Jun 30:2023.06.29.546885. doi: , 10.1101/2023.06.29.546885. PMID:37425880<ref>PMID:37425880</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 8th1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8th1" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[3D structures of G3BP|3D structures of G3BP]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Crystal Structure of the G3BP1 NTF2-like domain bound to the IDR1 of SARS-CoV-2 nucleocapsid protein D3L mutant
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