6R0T

Getah virus macro domain in complex with ADPr in open conformation

Summary for 6R0T

• Entry DOI: 10.2210/pdb6r0t/pdb
• Descriptor: Non-structural polyprotein, [[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] [(2~{R},3~{S},4~{S})-2,3,4,5-tetrakis(oxidanyl)pentyl] hydrogen phosphate, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: macro domain, getah virus, viral protein
• Biological source: Getah virus (GETV)
• Total number of polymer chains: 2
• Total formula weight: 37730.05

Authors

Ferreira Ramos, A.S.,Sulzenbacher, G.,Coutard, B. (deposition date: 2019-03-13, release date: 2020-04-01, Last modification date: 2024-01-31)

Primary citation

Ferreira-Ramos, A.S.,Sulzenbacher, G.,Canard, B.,Coutard, B.
Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography.
Sci Rep, 10:14422-14422, 2020

PubMed 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.

PubMed: 32879358
DOI: 10.1038/s41598-020-70870-w

Experimental method

X-RAY DIFFRACTION (1.85 Å)