期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 503, 期 2, 页码 938-943出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.06.099
关键词
Endoplasmic reticulum; ER-Associated degradation; Oxido-reductase; Protein folding and quality control; TMX1; Ubiquitin proteasome system
资金
- Swiss National Science Foundation [31003A_163063]
- Signora Alessandra
- AlphaONE Foundation
- Foundation for Research on Neurodegenerative Diseases
- Novartis Foundation
- Comel Foundation
- Gelu Foundation
The Endoplasmic Reticulum (ER) is site of production of secretory and membrane proteins in eukaryotic cells. The ER does not contain catabolic devices and misfolded proteins generated in its lumen must be dislocated across the ER membrane before clearance by cytosolic proteasomes (ER-Associated Degradation, ERAD). How misfolded proteins are dislocated across the ER membrane is a matter of controversy. For example, it remains to be established if polypeptide unfolding is always required. If unfolding is a pre-requisite for dislocation as emerging evidences seem to indicate, it is likely that the incorrect set of disulfide bonds established during unsuccessful folding-attempts that precede selection for ERAD must be reduced to eliminate tertiary and quaternary structures that could hamper dislocation. The lumen of the mammalian ER contains more than 20 members of the PDI family, a handful of which plays a role in ERAD. Here we add the atypical, membrane-bound reductase TMX1 to this list and we show that TMX1 preferentially acts on membrane-tethered folding-defective polypeptides essentially ignoring the same misfolded ectodomains, when not associated to the ER membrane. As such, TMX1 is the first example of a topology-specific client protein redox catalyst acting both in the folding and in the degradative pathways. (C) 2018 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据