Inside-out: antibody-binding reveals potential folding hinge-points within the SARS-CoV-2 replication co-factor nsp9

Pan, Yue, Chandrashekaran, Indu R., Tennant, Luke, Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 and Littler, Dene R. 2023. Inside-out: antibody-binding reveals potential folding hinge-points within the SARS-CoV-2 replication co-factor nsp9. PLoS ONE 18 (4) , e0283194. 10.1371/journal.pone.0283194

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Abstract

Nsp9 is a conserved accessory component of the coronaviral replication and transcription complex. It is the predominant substrate of nsp12’s nucleotidylation activity while also serving to recruit proteins required for viral 5’-capping. Anti-nsp9 specific nanobodies have been isolated previously. We confirm that their binding mode is centred upon Trp-53 within SARS-CoV-2 nsp9. Antibody binding at this site surprisingly results in large-scale changes to the overall topology of this coronaviral unique fold. We further characterise the antibody-induced structural dynamism within nsp9, identifying a number of potentially flexible regions. A large expansion of the cavity between the s2-s3 and s4-s5 loops is particularly noteworthy. As is the potential for large-scale movements in the C-terminal GxxxG helix.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/
Publisher:	Public Library of Science
Date of First Compliant Deposit:	11 April 2023
Date of Acceptance:	3 March 2023
Last Modified:	28 May 2023 03:09
URI:	https://orca.cardiff.ac.uk/id/eprint/158525

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