Nicholas R Guydosh, Philipp Kimmig ... Rachel Green
A critical component of the cellular response to unfolded proteins is the widespread rescue of ribosomes that stall on endonucleolytically-cleaved mRNA transcripts.
G Elif Karagöz, Diego Acosta-Alvear ... Peter Walter
ER-stress sensing mechanism of the unfolded protein response sensor/transducer IRE1 is conserved from yeast to mammals, where in mammals, unfolded protein binding to IRE1's ER lumenal domain is coupled to its oligomerization and activation through an allosteric conformational change.
Client protein-driven reversal of endoplasmic reticulum chaperone (BiP) mediated-repression is revealed as a principal component of the regulation of the unfolded protein response transducer IRE1 in cells.
Diego Acosta-Alvear, G Elif Karagöz ... Peter Walter
The coordination of protein targeting to the endoplasmic reticulum and the unfolded protein response through the stress sensor IRE1 ensures quality control of the secreted and transmembrane proteomes.
The chaperone protein BiP forms complexes with Ire1 and Perk that dissociate when unfolded proteins bind to BiP to activate the unfolded protein response in the ER.
Quantitative FRET UPR induction assay is used to measure IRE1 and BIP association and dissociation by a variety of ER misfolded proteins and by an important BiP substrate-binding domain mutant, significantly enhancing the evidence for the allosteric UPR induction model.
Vladislav Belyy, Iratxe Zuazo-Gaztelu ... Peter Walter
Stress sensors in the membrane of the endoplasmic reticulum respond to the accumulation of unfolded proteins by briefly forming small phosphorylation-competent oligomers and dissolving back into active dimers.
Biochemical analysis and computational modeling reveal how cells mechanistically control the quality of their proteomes and demonstrate that the precise alignment of subunits in oligomeric complexes can profoundly affect enzymatic properties.
