5TXK

CRYSTAL STRUCTURE OF USP35 C450S IN COMPLEX WITH UBIQUITIN

5TXK の概要

• エントリーDOI: 10.2210/pdb5txk/pdb
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 35,Ubiquitin carboxyl-terminal hydrolase 35, Polyubiquitin-B, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: deubiquitinase, 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: 50855.78

構造登録者

Bader, G.,Weiss-Puxbaum, A.,Zoephel, A. (登録日: 2016-11-17, 公開日: 2018-05-09, 最終更新日: 2024-05-08)

主引用文献

Leznicki, P.,Natarajan, J.,Bader, G.,Spevak, W.,Schlattl, A.,Abdul Rehman, S.A.,Pathak, D.,Weidlich, S.,Zoephel, A.,Bordone, M.C.,Barbosa-Morais, N.L.,Boehmelt, G.,Kulathu, Y.
Expansion of DUB functionality generated by alternative isoforms - USP35, a case study.
J. Cell. Sci., 131:-, 2018

PubMed Abstract: Protein ubiquitylation is a dynamic post-translational modification that can be reversed by deubiquitylating enzymes (DUBs). It is unclear how the small number (∼100) of DUBs present in mammalian cells regulate the thousands of different ubiquitylation events. Here, we analysed annotated transcripts of human DUBs and found ∼300 ribosome-associated transcripts annotated as protein coding, which thus increases the total number of DUBs. By using USP35, a poorly studied DUB, as a case study, we provide evidence that alternative isoforms contribute to the functional expansion of DUBs. We show that there are two different USP35 isoforms that localise to different intracellular compartments and have distinct functions. Our results reveal that isoform 1 is an anti-apoptotic factor that inhibits staurosporine- and TNF-related apoptosis-inducing ligand (TRAIL; also known as TNFSF10)-induced apoptosis. In contrast, USP35 isoform 2 is an integral membrane protein of the endoplasmic reticulum (ER) that is also present at lipid droplets. Manipulations of isoform 2 levels cause rapid ER stress, likely through deregulation of lipid homeostasis, and lead to cell death. Our work highlights how alternative isoforms provide functional expansion of DUBs and sets directions for future research.This article has an associated First Person interview with the first author of the paper.

PubMed: 29685892
DOI: 10.1242/jcs.212753

実験手法

X-RAY DIFFRACTION (1.84 Å)