6R0R

Getah virus macro domain in complex with ADPr covalently bond to Cys34

6R0R の概要

• エントリーDOI: 10.2210/pdb6r0r/pdb
• 分子名称: 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, ... (4 entities in total)
• 機能のキーワード: macro domain, getah virus, viral protein
• 由来する生物種: Getah virus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18743.91

構造登録者

Ferreira Ramos, A.S.,Sulzenbacher, G.,Coutard, B. (登録日: 2019-03-13, 公開日: 2020-04-01, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.45 Å)