Universität zu Köln

Siva, Monika, Svoboda, Michal, Veverka, Vaclav ORCID: 0000-0003-3782-5279, Trempe, Jean-Francois, Hofmann, Kay, Kozisek, Milan ORCID: 0000-0002-9476-3409, Hexnerova, Rozalie ORCID: 0000-0002-3537-8439, Sedlak, Frantisek ORCID: 0000-0002-5565-8462, Belza, Jan ORCID: 0000-0002-3104-6007, Brynda, Jiri ORCID: 0000-0003-3675-6769, Sacha, Pavel ORCID: 0000-0001-6198-9826, Hubalek, Martin, Starkova, Jana, Flaisigova, Iva, Konvalinka, Jan ORCID: 0000-0003-0695-9266 and Saskova, Klara Grantz ORCID: 0000-0003-2874-5699 (2016). Human DNA-Damage-Inducible 2 Protein Is Structurally and Functionally Distinct from Its Yeast Ortholog. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Siva, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Svoboda, Michal UNSPECIFIED UNSPECIFIED UNSPECIFIED Veverka, Vaclav UNSPECIFIED orcid.org/0000-0003-3782-5279 UNSPECIFIED Trempe, Jean-Francois UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Kay UNSPECIFIED UNSPECIFIED UNSPECIFIED Kozisek, Milan UNSPECIFIED orcid.org/0000-0002-9476-3409 UNSPECIFIED Hexnerova, Rozalie UNSPECIFIED orcid.org/0000-0002-3537-8439 UNSPECIFIED Sedlak, Frantisek UNSPECIFIED orcid.org/0000-0002-5565-8462 UNSPECIFIED Belza, Jan UNSPECIFIED orcid.org/0000-0002-3104-6007 UNSPECIFIED Brynda, Jiri UNSPECIFIED orcid.org/0000-0003-3675-6769 UNSPECIFIED Sacha, Pavel UNSPECIFIED orcid.org/0000-0001-6198-9826 UNSPECIFIED Hubalek, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Starkova, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Flaisigova, Iva UNSPECIFIED UNSPECIFIED UNSPECIFIED Konvalinka, Jan UNSPECIFIED orcid.org/0000-0003-0695-9266 UNSPECIFIED Saskova, Klara Grantz UNSPECIFIED orcid.org/0000-0003-2874-5699 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-269506
DOI:	10.1038/srep30443
Journal or Publication Title:	Sci Rep
Volume:	6
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language UBIQUITIN RECEPTOR; PEPTIDE LIBRARIES; DDI1; REGULATOR; DOMAINS; ELECTROSTATICS; RECOGNITION; ASSIGNMENT; PROTEASES; CLEAVAGE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26950