7LEW

Crystal structure of UBE2G2 in complex with the UBE2G2-binding region of AUP1

7LEW の概要

• エントリーDOI: 10.2210/pdb7lew/pdb
• 分子名称: Ubiquitin-conjugating enzyme E2 G2, Lipid droplet-regulating VLDL assembly factor AUP1 (3 entities in total)
• 機能のキーワード: alpha beta, ligase, ligase-transferase complex, ligase/transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22773.85

構造登録者

Liang, Y.-H.,Smith, C.E.,Tsai, Y.C.,Weissman, A.M.,Ji, X. (登録日: 2021-01-15, 公開日: 2021-11-10, 最終更新日: 2023-10-18)

主引用文献

Smith, C.E.,Tsai, Y.C.,Liang, Y.H.,Khago, D.,Mariano, J.,Li, J.,Tarasov, S.G.,Gergel, E.,Tsai, B.,Villaneuva, M.,Clapp, M.E.,Magidson, V.,Chari, R.,Byrd, R.A.,Ji, X.,Weissman, A.M.
A structurally conserved site in AUP1 binds the E2 enzyme UBE2G2 and is essential for ER-associated degradation.
Plos Biol., 19:e3001474-e3001474, 2021

PubMed Abstract: Endoplasmic reticulum-associated degradation (ERAD) is a protein quality control pathway of fundamental importance to cellular homeostasis. Although multiple ERAD pathways exist for targeting topologically distinct substrates, all pathways require substrate ubiquitination. Here, we characterize a key role for the UBE2G2 Binding Region (G2BR) of the ERAD accessory protein ancient ubiquitous protein 1 (AUP1) in ERAD pathways. This 27-amino acid (aa) region of AUP1 binds with high specificity and low nanomolar affinity to the backside of the ERAD ubiquitin-conjugating enzyme (E2) UBE2G2. The structure of the AUP1 G2BR (G2BRAUP1) in complex with UBE2G2 reveals an interface that includes a network of salt bridges, hydrogen bonds, and hydrophobic interactions essential for AUP1 function in cells. The G2BRAUP1 shares significant structural conservation with the G2BR found in the E3 ubiquitin ligase gp78 and in vitro can similarly allosterically activate ubiquitination in conjunction with ERAD E3s. In cells, AUP1 is uniquely required to maintain normal levels of UBE2G2; this is due to G2BRAUP1 binding to the E2 and preventing its rapid degradation. In addition, the G2BRAUP1 is required for both ER membrane recruitment of UBE2G2 and for its activation at the ER membrane. Thus, by binding to the backside of a critical ERAD E2, G2BRAUP1 plays multiple critical roles in ERAD.

PubMed: 34879065
DOI: 10.1371/journal.pbio.3001474

実験手法

X-RAY DIFFRACTION (1.736 Å)