2GJD

Distinct functional domains of Ubc9 dictate cell survival and resistance to genotoxic stress

2GJD の概要

• エントリーDOI: 10.2210/pdb2gjd/pdb
• 関連するPDBエントリー: 1A3S 1U9A
• 分子名称: Ubiquitin-conjugating enzyme E2-18 kDa (2 entities in total)
• 機能のキーワード: ubc9p, e2, smt3, saccharomyces cerevisiae, ligase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• 細胞内の位置: Nucleus: P50623
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 71745.69

構造登録者

van Waardenburg, R.C.,Duda, D.M.,Lancaster, C.S.,Schulman, B.A.,Bjornsti, M.A. (登録日: 2006-03-30, 公開日: 2006-07-04, 最終更新日: 2023-08-30)

主引用文献

van Waardenburg, R.C.,Duda, D.M.,Lancaster, C.S.,Schulman, B.A.,Bjornsti, M.A.
Distinct functional domains of ubc9 dictate cell survival and resistance to genotoxic stress.
Mol.Cell.Biol., 26:4958-4969, 2006

PubMed Abstract: Covalent modification with SUMO alters protein function, intracellular localization, or protein-protein interactions. Target recognition is determined, in part, by the SUMO E2 enzyme, Ubc9, while Siz/Pias E3 ligases may facilitate select interactions by acting as substrate adaptors. A yeast conditional Ubc9P(123)L mutant was viable at 36 degrees C yet exhibited enhanced sensitivity to DNA damage. To define functional domains in Ubc9 that dictate cellular responses to genotoxic stress versus those necessary for cell viability, a 1.75-A structure of yeast Ubc9 that demonstrated considerable conservation of backbone architecture with human Ubc9 was solved. Nevertheless, differences in side chain geometry/charge guided the design of human/yeast chimeras, where swapping domains implicated in (i) binding residues within substrates that flank canonical SUMOylation sites, (ii) interactions with the RanBP2 E3 ligase, and (iii) binding of the heterodimeric E1 and SUMO had distinct effects on cell growth and resistance to DNA-damaging agents. Our findings establish a functional interaction between N-terminal and substrate-binding domains of Ubc9 and distinguish the activities of E3 ligases Siz1 and Siz2 in regulating cellular responses to genotoxic stress.

PubMed: 16782883
DOI: 10.1128/MCB.00160-06

実験手法

X-RAY DIFFRACTION (1.75 Å)