Human DNA-Damage-Inducible 2 Protein Is Structurally and Functionally Distinct from Its Yeast Ortholog

Sivá, Monika; Svoboda, Michal; Veverka, Václav; Trempe, J. F.; Hofmann, K.; Kožíšek, Milan; Hexnerová, Rozálie; Sedlák, František; Belza, Jan; Brynda, Jiří; Šácha, Pavel; Hubálek, Martin; Starková, Jana; Flaisigová, Iva; Konvalinka, Jan; Grantz Šašková, Klára

doi:https://dx.doi.org/10.1038/srep30443

Number of the records: 1

Human DNA-Damage-Inducible 2 Protein Is Structurally and Functionally Distinct from Its Yeast Ortholog

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SYSNO ASEP	0463511
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Human DNA-Damage-Inducible 2 Protein Is Structurally and Functionally Distinct from Its Yeast Ortholog
Author(s)	Sivá, Monika (UOCHB-X)_{RID, ORCID} Svoboda, Michal (UOCHB-X)_RID Veverka, Václav (UOCHB-X)_{RID, ORCID} Trempe, J. F. (CA) Hofmann, K. (DE) Kožíšek, Milan (UOCHB-X)_{RID, ORCID} Hexnerová, Rozálie (UOCHB-X)_{ORCID, RID} Sedlák, František (UOCHB-X)_{RID, ORCID} Belza, Jan (UOCHB-X) Brynda, Jiří (UOCHB-X)_{RID, ORCID} Šácha, Pavel (UOCHB-X)_{RID, ORCID} Hubálek, Martin (UOCHB-X)_{RID, ORCID} Starková, Jana (UOCHB-X) Flaisigová, Iva (UOCHB-X) Konvalinka, Jan (UOCHB-X)_{RID, ORCID} Grantz Šašková, Klára (UOCHB-X)_{RID, ORCID}
Article number	30443
Source Title	Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322 Roč. 6, Jul 27 (2016)
Number of pages	15 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	human DNA-damage-inducible 2 protein ; proteasome ; ubiquitin ; retroviral protease-like domain
Subject RIV	CE - Biochemistry
R&D Projects	GBP208/12/G016 GA ČR - Czech Science Foundation (CSF)
Institutional support	UOCHB-X - RVO:61388963
UT WOS	000380331500001
EID SCOPUS	84980002308
DOI	10.1038/srep30443
Annotation	Although Ddi1-like proteins are conserved among eukaryotes, their biological functions remain poorly characterized. Yeast Ddi1 has been implicated in cell cycle regulation, DNA-damage response, and exocytosis. By virtue of its ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains, it has been proposed to serve as a proteasomal shuttle factor. All Ddi1-like family members also contain a highly conserved retroviral protease-like (RVP) domain with unknown substrate specificity. While the structure and biological function of yeast Ddi1 have been investigated, no such analysis is available for the human homologs. To address this, we solved the 3D structures of the human Ddi2 UBL and RVP domains and identified a new helical domain that extends on either side of the RVP dimer. While Ddi1-like proteins from all vertebrates lack a UBA domain, we identify a novel ubiquitin-interacting motif (UIM) located at the C-terminus of the protein. The UIM showed a weak yet specific affinity towards ubiquitin, as did the Ddi2 UBL domain. However, the full-length Ddi2 protein is unable to bind to di-ubiquitin chains. While proteomic analysis revealed no activity, implying that the protease requires other factors for activation, our structural characterization of all domains of human Ddi2 sets the stage for further characterization.
Workplace	Institute of Organic Chemistry and Biochemistry
Contact	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Year of Publishing	2017
Electronic address	http://www.nature.com/articles/srep30443

Number of the records: 1