4Z2Z

New crystal structure of yeast Ddi1 aspartyl protease reveals substrate engagement mode

4Z2Z の概要

• エントリーDOI: 10.2210/pdb4z2z/pdb
• 分子名称: DNA damage-inducible protein 1 (2 entities in total)
• 機能のキーワード: protease, ddi1, hydrolase
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32663.94

構造登録者

Trempe, J.-F.,Feng, X.,Gehring, K. (登録日: 2015-03-30, 公開日: 2016-04-13, 最終更新日: 2023-09-27)

主引用文献

Trempe, J.F.,Saskova, K.G.,Siva, M.,Ratcliffe, C.D.,Veverka, V.,Hoegl, A.,Menade, M.,Feng, X.,Shenker, S.,Svoboda, M.,Kozisek, M.,Konvalinka, J.,Gehring, K.
Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family.
Sci Rep, 6:33671-33671, 2016

PubMed Abstract: The eukaryotic Ddi1 family is defined by a conserved retroviral aspartyl protease-like (RVP) domain found in association with a ubiquitin-like (UBL) domain. Ddi1 from Saccharomyces cerevisiae additionally contains a ubiquitin-associated (UBA) domain. The substrate specificity and role of the protease domain in the biological functions of the Ddi family remain unclear. Yeast Ddi1 has been implicated in the regulation of cell cycle progression, DNA-damage repair, and exocytosis. Here, we investigated the multi-domain structure of yeast Ddi1 using X-ray crystallography, nuclear magnetic resonance, and small-angle X-ray scattering. The crystal structure of the RVP domain sheds light on a putative substrate recognition site involving a conserved loop. Isothermal titration calorimetry confirms that both UBL and UBA domains bind ubiquitin, and that Ddi1 binds K48-linked diubiquitin with enhanced affinity. The solution NMR structure of a helical domain that precedes the protease displays tertiary structure similarity to DNA-binding domains from transcription regulators. Our structural studies suggest that the helical domain could serve as a landing platform for substrates in conjunction with attached ubiquitin chains binding to the UBL and UBA domains.

PubMed: 27646017
DOI: 10.1038/srep33671

実験手法

X-RAY DIFFRACTION (1.8 Å)