% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @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}, }