3ZNZ

Crystal structure of OTULIN OTU domain (C129A) in complex with Met1- di ubiquitin

3ZNZ の概要

• エントリーDOI: 10.2210/pdb3znz/pdb
• 関連するPDBエントリー: 3ZNV 3ZNX
• 分子名称: PROTEIN FAM105B, POLYUBIQUITIN-C, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: hydrolase
• 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: 49702.68

構造登録者

Keusekotten, K.,Elliott, P.R.,Glockner, L.,Kulathu, Y.,Wauer, T.,Krappmann, D.,Hofmann, K.,Komander, D. (登録日: 2013-02-18, 公開日: 2013-06-26, 最終更新日: 2023-12-20)

主引用文献

Keusekotten, K.,Elliott, P.R.,Glockner, L.,Fiil, B.K.,Damgaard, R.B.,Kulathu, Y.,Wauer, T.,Hospenthal, M.K.,Gyrd-Hansen, M.,Krappmann, D.,Hofmann, K.,Komander, D.
Otulin Antagonizes Lubac Signaling by Specifically Hydrolyzing met1-Linked Polyubiquitin.
Cell(Cambridge,Mass.), 153:1312-, 2013

PubMed Abstract: The linear ubiquitin (Ub) chain assembly complex (LUBAC) is an E3 ligase that specifically assembles Met1-linked (also known as linear) Ub chains that regulate nuclear factor κB (NF-κB) signaling. Deubiquitinases (DUBs) are key regulators of Ub signaling, but a dedicated DUB for Met1 linkages has not been identified. Here, we reveal a previously unannotated human DUB, OTULIN (also known as FAM105B), which is exquisitely specific for Met1 linkages. Crystal structures of the OTULIN catalytic domain in complex with diubiquitin reveal Met1-specific Ub-binding sites and a mechanism of substrate-assisted catalysis in which the proximal Ub activates the catalytic triad of the protease. Mutation of Ub Glu16 inhibits OTULIN activity by reducing kcat 240-fold. OTULIN overexpression or knockdown affects NF-κB responses to LUBAC, TNFα, and poly(I:C) and sensitizes cells to TNFα-induced cell death. We show that OTULIN binds LUBAC and that overexpression of OTULIN prevents TNFα-induced NEMO association with ubiquitinated RIPK1. Our data suggest that OTULIN regulates Met1-polyUb signaling.

PubMed: 23746843
DOI: 10.1016/J.CELL.2013.05.014

実験手法

X-RAY DIFFRACTION (1.9 Å)