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

Ana Sofia Ferreira-Ramos, Gerlind Sulzenbacher*, Bruno Canard, Bruno Coutard

*Corresponding author for this work
1 Citation (Scopus)

Abstract

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 zinc-binding 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.

Original languageEnglish
Article number14422
JournalScientific Reports
Volume10
Issue number1
ISSN2045-2322
DOIs
Publication statusPublished - 01.12.2020

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

  • 201-01 Biochemistry

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