Lalić, Jasna; Posavec Marjanović, Melanija; Palazzo, Luca; Perina, Dragutin; Sabljić, Igor; Žaja, Roko; Colby, Thomas; Pleše, Bruna; Halasz, Mirna; Jankevicius, Gytis; Bucca, Giselda; Ahel, Marijan; Matić, Ivan; Ćetković, Helena; Luić, Marija; Mikoč, Andreja; Ahel, Ivan (2017) Disruption of macrodomain protein SCO6735 increases antibiotic production in Streptomyces coelicolor. Journal of Biological Chemistry, 291 (44). pp. 23175-23187. ISSN 0021-9258
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Abstract
ADP-ribosylation is a post-translational modification that can alter the physical and chemical properties of target proteins and controls many important cellular processes. Macrodomains are evolutionarily conserved structural domains that bind ADP-ribose derivatives and are found in proteins with diverse cellular functions. Some proteins from the macrodomain family can hydrolyze ADP- ribosylated substrates and therefore reverse this post-translational modification. Bacteria and Streptomyces, in particular, are known to utilize protein ADP-ribosylation, yet very little is known about their enzymes that synthesise and remove this modification. We have determined the crystal structure and characterized, both biochemically and functionally, the macrodomain protein SCO6735 from Streptomyces coelicolor. This protein is a member of an uncharacterised subfamily of macrodomain proteins. Its crystal structure revealed a highly conserved macrodomain fold. We showed that SCO6735 possesses the ability to hydrolyse PARP-dependent protein ADP- ribosylation. Furthermore, we showed that expression of this protein is induced upon DNA damage and that deletion of this protein in S. coelicolor increases antibiotic production. Our results provide the first insights into the molecular basis of its action and impact on Streptomyces metabolism.
| Item Type: | Article |
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| Additional Information: | This work was supported by Unity through Knowledge Fund Grant UKF 1B 2/13, European Research Council Grant 281739, Wellcome Trust Grant 101794, Cancer Research UK Grant C35050/A22284, and European Community's Seventh Framework Programme FP7/2007-2013 under BioStruct-X Grant 283570. The authors declare that they have no conflicts of interest with the contents of this article. |
| Uncontrolled Keywords: | ADP-ribosylation ; actinobacteria ; antibiotics ; protein structure ; macrodomain ; PARP ; PARG ; DNA damage response ; Streptomyces |
| Subjects: | NATURAL SCIENCES > Biology |
| Divisions: | Division for Marine and Enviromental Research Division of Molecular Biology Division of Physical Chemistry |
| Depositing User: | Igor Sabljić |
| Date Deposited: | 30 Nov 2017 11:48 |
| URI: | http://fulir.irb.hr/id/eprint/3694 |
| DOI: | 10.1074/jbc.M116.721894 |
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