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Article Dans Une Revue Scientific Reports Année : 2020

Snapshots of ADp-ribose bound to Getah virus macro domain reveal an intriguing choreography

Résumé

Alphaviruses are (re-)emerging arboviruses of public health concern. The nsP3 gene product is one of the key players during viral replication. NsP3 comprises three domains: a macro domain, a zincbinding domain and a hypervariable region. the macro domain is essential at both early and late stages of the replication cycle through ADp-ribose (ADpr) binding and de-ADp-ribosylation of host proteins. However, both its specific role and the precise molecular mechanism of de-ADP-ribosylation across specific viral families remains to be elucidated. Here we investigate by X-ray crystallography the mechanism of ADPr reactivity in the active site of Getah virus macro domain, which displays a peculiar substitution of one of the conserved residues in the catalytic loop. ADpr adopts distinct poses including a covalent bond between the c′′1 of the ADPr and a conserved Togaviridae-specific cysteine. These different poses observed for ADPr may represent snapshots of the de-ADP-ribosylation mechanism, highlighting residues to be further characterised.
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hal-03160433 , version 1 (05-03-2021)

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Ana Sofia Ferreira-Ramos, Gerlind Sulzenbacher, Bruno Canard, Bruno Coutard. Snapshots of ADp-ribose bound to Getah virus macro domain reveal an intriguing choreography. Scientific Reports, 2020, 10 (1), ⟨10.1038/s41598-020-70870-w⟩. ⟨hal-03160433⟩
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