3UGB

UbcH5c~Ubiquitin Conjugate

3UGB の概要

• エントリーDOI: 10.2210/pdb3ugb/pdb
• 関連するPDBエントリー: 1fxt 2gmi 2kjh 3a33 3jw0
• 分子名称: Ubiquitin-conjugating enzyme E2 D3, Polyubiquitin-C, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: e2 ubiquitin-conjugating enzyme, ubiquitin, ubl conjugation pathway, oxyester bond, ubiquitin-protein ligase activity, ligase-protein binding complex, ligase/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane; Peripheral membrane protein: P61077; Ubiquitin: Cytoplasm (By similarity): P0CG48
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25451.09

構造登録者

Page, R.C.,Pruneda, J.N.,Klevit, R.E.,Misra, S. (登録日: 2011-11-02, 公開日: 2012-05-16, 最終更新日: 2024-11-06)

主引用文献

Page, R.C.,Pruneda, J.N.,Amick, J.,Klevit, R.E.,Misra, S.
Structural insights into the conformation and oligomerization of E2~ubiquitin conjugates.
Biochemistry, 51:4175-4187, 2012

PubMed Abstract: Post-translational modification of proteins by ubiquitin (Ub) regulates a host of cellular processes, including protein quality control, DNA repair, endocytosis, and cellular signaling. In the ubiquitination cascade, a thioester-linked conjugate between the C-terminus of Ub and the active site cysteine of a ubiquitin-conjugating enzyme (E2) is formed. The E2~Ub conjugate interacts with a ubiquitin ligase (E3) to transfer Ub to a lysine residue on a target protein. The flexibly linked E2~Ub conjugates have been shown to form a range of structures in solution. In addition, select E2~Ub conjugates oligomerize through a noncovalent "backside" interaction between Ub and E2 components of different conjugates. Additional studies are needed to bridge the gap between the dynamic monomeric conjugates, E2~Ub oligomers, and the mechanisms of ubiquitination. We present a new 2.35 Å crystal structure of an oligomeric UbcH5c~Ub conjugate. The conjugate forms a staggered linear oligomer that differs substantially from the "infinite spiral" helical arrangement of the only previously reported structure of an oligomeric conjugate. Our structure also differs in intraconjugate conformation from other structurally characterized conjugates. Despite these differences, we find that the backside interaction mode is conserved in different conjugate oligomers and is independent of intraconjugate relative E2-Ub orientations. We delineate a common intraconjugate E2-binding surface on Ub. In addition, we demonstrate that an E3 CHIP (carboxyl terminus of Hsp70 interacting protein) interacts directly with UbcH5c~Ub oligomers, not only with conjugate monomers. These results provide insights into the conformational diversity of E2~Ub conjugates and conjugate oligomers, and into their compatibility and interactions with E3s, which have important consequences for the ubiquitination process.

PubMed: 22551455
DOI: 10.1021/bi300058m

実験手法

X-RAY DIFFRACTION (2.35 Å)