4P0A

Crystal structure of HOIP PUB domain in complex with p97 PIM

4P0A の概要

• エントリーDOI: 10.2210/pdb4p0a/pdb
• 分子名称: E3 ubiquitin-protein ligase RNF31, Transitional endoplasmic reticulum ATPase (3 entities in total)
• 機能のキーワード: hoip, pub domain, p97, pim, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : Q96EP0; Cytoplasm, cytosol : P55072
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 43854.88

構造登録者

Akutsu, M.,Schaeffer, V.,Olma, M.H.,Gomes, L.C.,Kawasaki, M.,Dikic, I. (登録日: 2014-02-20, 公開日: 2014-05-07, 最終更新日: 2024-10-23)

主引用文献

Schaeffer, V.,Akutsu, M.,Olma, M.H.,Gomes, L.C.,Kawasaki, M.,Dikic, I.
Binding of OTULIN to the PUB domain of HOIP controls NF-kappa B signaling.
Mol.Cell, 54:349-361, 2014

PubMed Abstract: Linear ubiquitin chains are implicated in the regulation of the NF-κB pathway, immunity, and inflammation. They are synthesized by the LUBAC complex containing the catalytic subunit HOIL-1-interacting protein (HOIP) and are disassembled by the linear ubiquitin-specific deubiquitinase OTULIN. Little is known about the regulation of these opposing activities. Here we demonstrate that HOIP and OTULIN interact and act as a bimolecular editing pair for linear ubiquitin signals in vivo. The HOIP PUB domain binds to the PUB interacting motif (PIM) of OTULIN and the chaperone VCP/p97. Structural studies revealed the basis of high-affinity interaction with the OTULIN PIM. The conserved Tyr56 of OTULIN makes critical contacts with the HOIP PUB domain, and its phosphorylation negatively regulates this interaction. Functionally, HOIP binding to OTULIN is required for the recruitment of OTULIN to the TNF receptor complex and to counteract HOIP-dependent activation of the NF-κB pathway.

PubMed: 24726327
DOI: 10.1016/j.molcel.2014.03.016

実験手法

X-RAY DIFFRACTION (2.3001 Å)