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@ARTICLE{Eckei:830504,
author = {Eckei, Laura and Krieg, Sarah and Bütepage, Mareike and
Lehmann, Anne and Gross, Annika and Lippok, Barbara and
Grimm, Alexander R. and Kümmerer, Beate M. and Rossetti,
Giulia and Lüscher, Bernhard and Verheugd, Patricia},
title = {{T}he conserved macrodomains of the non-structural proteins
of {C}hikungunya virus and other pathogenic positive strand
{RNA} viruses function as mono-{ADP}-ribosylhydrolases},
journal = {Scientific reports},
volume = {7},
issn = {2045-2322},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2017-04045},
pages = {41746 -},
year = {2017},
abstract = {Human pathogenic positive single strand RNA ((+)ssRNA)
viruses, including Chikungunya virus, pose severe health
problems as for many neither efficient vaccines nor
therapeutic strategies exist. To interfere with propagation,
viral enzymatic activities are considered potential targets.
Here we addressed the function of the viral macrodomains,
conserved folds of non-structural proteins of many (+)ssRNA
viruses. Macrodomains are closely associated with ADP-ribose
function and metabolism. ADP-ribosylation is a
post-translational modification controlling various cellular
processes, including DNA repair, transcription and stress
response. We found that the viral macrodomains possess broad
hydrolase activity towards mono-ADP-ribosylated substrates
of the mono-ADP-ribosyltransferases ARTD7, ARTD8 and ARTD10
(aka PARP15, PARP14 and PARP10, respectively), reverting
this post-translational modification both in vitro and in
cells. In contrast, the viral macrodomains possess only weak
activity towards poly-ADP-ribose chains synthesized by ARTD1
(aka PARP1). Unlike poly-ADP-ribosylglycohydrolase, which
hydrolyzes poly-ADP-ribose chains to individual ADP-ribose
units but cannot cleave the amino acid side chain -
ADP-ribose bond, the different viral macrodomains release
poly-ADP-ribose chains with distinct efficiency. Mutational
and structural analyses identified key amino acids for
hydrolase activity of the Chikungunya viral macrodomain.
Moreover, ARTD8 and ARTD10 are induced by innate immune
mechanisms, suggesting that the control of
mono-ADP-ribosylation is part of a host-pathogen conflict.},
cin = {IAS-5 / INM-9 / JSC},
ddc = {000},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121 /
I:(DE-Juel1)JSC-20090406},
pnm = {511 - Computational Science and Mathematical Methods
(POF3-511)},
pid = {G:(DE-HGF)POF3-511},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000393651900001},
pubmed = {pmid:28150709},
doi = {10.1038/srep41746},
url = {https://juser.fz-juelich.de/record/830504},
}