4TSE

Crystal Structure of the Mib Repeat Domain of Mind bomb 1

4TSE の概要

• エントリーDOI: 10.2210/pdb4tse/pdb
• 関連するPDBエントリー: 4TSG 4TSI 4TSJ
• 分子名称: E3 ubiquitin-protein ligase MIB1 (2 entities in total)
• 機能のキーワード: e3 ubiquitin ligase, notch pathway, ligase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37001.06

構造登録者

McMillan, B.J.,Blacklow, S.C. (登録日: 2014-06-18, 公開日: 2015-03-18, 最終更新日: 2023-12-27)

主引用文献

McMillan, B.J.,Schnute, B.,Ohlenhard, N.,Zimmerman, B.,Miles, L.,Beglova, N.,Klein, T.,Blacklow, S.C.
A tail of two sites: a bipartite mechanism for recognition of notch ligands by mind bomb e3 ligases.
Mol.Cell, 57:912-924, 2015

PubMed Abstract: Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. This ubiquitination step marks the ligand proteins for epsin-dependent endocytosis, which is critical for in vivo Notch receptor activation. We present here crystal structures of the substrate recognition domains of Mib1, both in isolation and in complex with peptides derived from Notch ligands. The structures, in combination with biochemical, cellular, and in vivo assays, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C terminus. Together, these studies provide insights into the mechanism of ubiquitin transfer by Mind bomb E3 ligases, illuminate a key event in ligand-induced activation of Notch receptors, and identify a potential target for therapeutic modulation of Notch signal transduction in disease.

PubMed: 25747658
DOI: 10.1016/j.molcel.2015.01.019

実験手法

X-RAY DIFFRACTION (2.057 Å)