1TT5

Structure of APPBP1-UBA3-Ubc12N26: a unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8

1TT5 の概要

• エントリーDOI: 10.2210/pdb1tt5/pdb
• 分子名称: amyloid protein-binding protein 1, ubiquitin-activating enzyme E1C isoform 1, Ubiquitin-conjugating enzyme E2 M, ... (5 entities in total)
• 機能のキーワード: cell cycle, ligase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 223428.73

構造登録者

Huang, D.T.,Miller, D.W.,Mathew, R.,Cassell, R.,Holton, J.M.,Roussel, M.F.,Schulman, B.A. (登録日: 2004-06-21, 公開日: 2004-09-14, 最終更新日: 2024-02-14)

主引用文献

Huang, D.T.,Miller, D.W.,Mathew, R.,Cassell, R.,Holton, J.M.,Roussel, M.F.,Schulman, B.A.
A unique E1-E2 interaction required for optimal conjugation of the ubiquitin-like protein NEDD8.
Nat.Struct.Mol.Biol., 11:927-935, 2004

PubMed Abstract: Ubiquitin-like proteins (UBLs) such as NEDD8 are transferred to their targets by distinct, parallel, multienzyme cascades that involve the sequential action of E1, E2 and E3 enzymes. How do enzymes within a particular UBL conjugation cascade interact with each other? We report here that the unique N-terminal sequence of NEDD8's E2, Ubc12, selectively recruits NEDD8's E1 to promote thioester formation between Ubc12 and NEDD8. A peptide corresponding to Ubc12's N terminus (Ubc12N26) specifically binds and inhibits NEDD8's E1, the heterodimeric APPBP1-UBA3 complex. The structure of APPBP1-UBA3- Ubc12N26 reveals conserved Ubc12 residues docking in a groove generated by loops conserved in UBA3s but not other E1s. These data explain why the Ubc12-UBA3 interaction is unique to the NEDD8 pathway. These studies define a novel mechanism for E1-E2 interaction and show how enzymes within a particular UBL conjugation cascade can be tethered together by unique protein-protein interactions emanating from their common structural scaffolds.

PubMed: 15361859
DOI: 10.1038/nsmb826

実験手法

X-RAY DIFFRACTION (2.6 Å)