8V0E

ANK repeat of MIB1

8V0E の概要

• エントリーDOI: 10.2210/pdb8v0e/pdb
• 分子名称: E3 ubiquitin-protein ligase MIB1, Unidentified MIB1 peptide (3 entities in total)
• 機能のキーワード: e3 ligase, ligase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 84290.21

構造登録者

Cao, R.,Blacklow, S.C. (登録日: 2023-11-17, 公開日: 2024-09-25, 最終更新日: 2024-10-16)

主引用文献

Cao, R.,Gozlan, O.,Airich, A.,Tveriakhina, L.,Zhou, H.,Jiang, H.,Cole, P.A.,Aster, J.C.,Klein, T.,Sprinzak, D.,Blacklow, S.C.
Structural requirements for activity of Mind bomb1 in Notch signaling.
Structure, 32:1667-1676.e5, 2024

PubMed Abstract: Mind bomb 1 (MIB1) is a RING E3 ligase that ubiquitinates Notch ligands, a necessary step for induction of Notch signaling. The structural basis for binding of the JAG1 ligand by the N-terminal region of MIB1 is known, yet how the ankyrin (ANK) and RING domains of MIB1 cooperate to catalyze ubiquitin transfer from E2∼Ub to Notch ligands remains unclear. Here, we show that the third RING domain and adjacent coiled coil region (ccRING3) drive MIB1 dimerization and that MIB1 ubiquitin transfer activity relies solely on ccRING3. We report X-ray crystal structures of a UbcH5B-ccRING3 complex and the ANK domain. Directly tethering the MIB1 N-terminal region to ccRING3 forms a minimal MIB1 protein sufficient to induce a Notch response in receiver cells and rescue mib knockout phenotypes in flies. Together, these studies define the functional elements of an E3 ligase needed for ligands to induce a Notch signaling response.

PubMed: 39121852
DOI: 10.1016/j.str.2024.07.011

実験手法

X-RAY DIFFRACTION (2.39 Å)