Activation of the Unfolded Protein Response by Lipid Bilayer Stress.
Mol Cell
; 67(4): 673-684.e8, 2017 Aug 17.
Article
em En
| MEDLINE
| ID: mdl-28689662
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Glicoproteínas de Membrana
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Proteínas Serina-Treonina Quinases
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Proteínas de Saccharomyces cerevisiae
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Retículo Endoplasmático
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Resposta a Proteínas não Dobradas
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Estresse do Retículo Endoplasmático
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Membranas Intracelulares
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Bicamadas Lipídicas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Alemanha