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:
CreatorsEmailORCIDORCID Put Code
Siva, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Svoboda, MichalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Veverka, VaclavUNSPECIFIEDorcid.org/0000-0003-3782-5279UNSPECIFIED
Trempe, Jean-FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, KayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kozisek, MilanUNSPECIFIEDorcid.org/0000-0002-9476-3409UNSPECIFIED
Hexnerova, RozalieUNSPECIFIEDorcid.org/0000-0002-3537-8439UNSPECIFIED
Sedlak, FrantisekUNSPECIFIEDorcid.org/0000-0002-5565-8462UNSPECIFIED
Belza, JanUNSPECIFIEDorcid.org/0000-0002-3104-6007UNSPECIFIED
Brynda, JiriUNSPECIFIEDorcid.org/0000-0003-3675-6769UNSPECIFIED
Sacha, PavelUNSPECIFIEDorcid.org/0000-0001-6198-9826UNSPECIFIED
Hubalek, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Starkova, JanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flaisigova, IvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konvalinka, JanUNSPECIFIEDorcid.org/0000-0003-0695-9266UNSPECIFIED
Saskova, Klara GrantzUNSPECIFIEDorcid.org/0000-0003-2874-5699UNSPECIFIED
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:
KeywordsLanguage
UBIQUITIN RECEPTOR; PEPTIDE LIBRARIES; DDI1; REGULATOR; DOMAINS; ELECTROSTATICS; RECOGNITION; ASSIGNMENT; PROTEASES; CLEAVAGEMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26950

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