未折叠蛋白反应
内质网
生物
脂质双层
细胞生物学
双层
生物物理学
蛋白质折叠
生物化学
膜
作者
Kristina Halbleib,Kristina Pesek,Roberto Covino,Harald F. Hofbauer,Dorith Wunnicke,Inga Hänelt,Gerhard Hummer,Robert Ernst
出处
期刊:Molecular Cell
[Elsevier]
日期:2017-08-01
卷期号:67 (4): 673-684.e8
被引量:240
标识
DOI:10.1016/j.molcel.2017.06.012
摘要
The unfolded protein response (UPR) is a conserved homeostatic program that is activated by misfolded proteins in the lumen of the endoplasmic reticulum (ER). Recently, it became evident that aberrant lipid compositions of the ER membrane, referred to as lipid bilayer stress, are equally potent in activating the UPR. The underlying molecular mechanism, however, remained unclear. We show that the most conserved transducer of ER stress, Ire1, uses an amphipathic helix (AH) to sense membrane aberrancies and control UPR activity. In vivo and in vitro experiments, together with molecular dynamics (MD) simulations, identify the physicochemical properties of the membrane environment that control Ire1 oligomerization. This work establishes the molecular mechanism of UPR activation by lipid bilayer stress.
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