8B9X

Chimeric protein of human UFM1 E3 ligase, UFL1, and DDRGK1

8B9X の概要

• エントリーDOI: 10.2210/pdb8b9x/pdb
• 分子名称: DDRGK domain-containing protein 1,E3 UFM1-protein ligase 1, CHLORIDE ION (3 entities in total)
• 機能のキーワード: post-translational modification, e3 ligases, signaling protein
• 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: 61823.32

構造登録者

Wiener, R.,Isupov, M.,banerjee, S. (登録日: 2022-10-10, 公開日: 2023-10-25, 最終更新日: 2026-03-04)

主引用文献

Banerjee, S.,Varga, J.K.,Kumar, M.,Zoltsman, G.,Rotem-Bamberger, S.,Cohen-Kfir, E.,Isupov, M.N.,Rosenzweig, R.,Schueler-Furman, O.,Wiener, R.
Structural study of UFL1-UFC1 interaction uncovers the role of UFL1 N-terminal helix in ufmylation.
Embo Rep., 24:e56920-e56920, 2023

PubMed Abstract: Ufmylation plays a crucial role in various cellular processes including DNA damage response, protein translation, and ER homeostasis. To date, little is known about how the enzymes responsible for ufmylation coordinate their action. Here, we study the details of UFL1 (E3) activity, its binding to UFC1 (E2), and its relation to UBA5 (E1), using a combination of structural modeling, X-ray crystallography, NMR, and biochemical assays. Guided by Alphafold2 models, we generate an active UFL1 fusion construct that includes its partner DDRGK1 and solve the crystal structure of this critical interaction. This fusion construct also unveiled the importance of the UFL1 N-terminal helix for binding to UFC1. The binding site suggested by our UFL1-UFC1 model reveals a conserved interface, and competition between UFL1 and UBA5 for binding to UFC1. This competition changes in the favor of UFL1 following UFM1 charging of UFC1. Altogether, our study reveals a novel, terminal helix-mediated regulatory mechanism, which coordinates the cascade of E1-E2-E3-mediated transfer of UFM1 to its substrate and provides new leads to target this modification.

PubMed: 37988244
DOI: 10.15252/embr.202356920

実験手法

X-RAY DIFFRACTION (3.066 Å)