TY - JOUR
T1 - Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography
AU - Ferreira-Ramos, Ana Sofia
AU - Sulzenbacher, Gerlind
AU - Canard, Bruno
AU - Coutard, Bruno
N1 - Funding Information:
We thank the European Synchrotron Radiation Facility (ESRF) and Synchrotron Soleil for beamtime allocation, and the staff of beamlines Proxima2, ID23-1 and ID30A-3 for assistance with data collection. This work was supported by the European Union Horizon 2020 Marie Skłodowska-Curie ETN “ANTIVIRALS” (Grant Agreement Number 642434) and by the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01. We thank Dr Karine Barral, Dr Sandrine Py and Dr Nicolas Papageorgiou for helpful discussions.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85090081217&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-70870-w
DO - 10.1038/s41598-020-70870-w
M3 - Journal articles
C2 - 32879358
AN - SCOPUS:85090081217
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 14422
ER -