2N7D

Solution structure of the UBL domain of human Ddi2

2N7D の概要

• エントリーDOI: 10.2210/pdb2n7d/pdb
• 関連するPDBエントリー: 2N7E
• NMR情報: BMRB: 25801
• 分子名称: Protein DDI1 homolog 2 (1 entity in total)
• 機能のキーワード: ddi2, unknown function
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11142.46

構造登録者

Siva, M.,Grantz Saskova, K.,Veverka, V. (登録日: 2015-09-08, 公開日: 2016-07-20, 最終更新日: 2024-05-15)

主引用文献

Siva, M.,Svoboda, M.,Veverka, V.,Trempe, J.F.,Hofmann, K.,Kozisek, M.,Hexnerova, R.,Sedlak, F.,Belza, J.,Brynda, J.,Sacha, P.,Hubalek, M.,Starkova, J.,Flaisigova, I.,Konvalinka, J.,Saskova, K.G.
Human DNA-Damage-Inducible 2 Protein Is Structurally and Functionally Distinct from Its Yeast Ortholog.
Sci Rep, 6:30443-30443, 2016

PubMed 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.

PubMed: 27461074
DOI: 10.1038/srep30443

実験手法

SOLUTION NMR