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Nat Commun. 2014 Jul 15;5:4383. doi: 10.1038/ncomms5383.

Loss of amino-terminal acetylation suppresses a prion phenotype by modulating global protein folding.

Author information

1
1] Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 185 Meeting Street, Providence, Rhode Island 02912, USA [2].
2
Graduate Interdisciplinary Program in Statistics, University of Arizona, 1548 East Drachman Street, Tucson, Arizona 85721, USA.
3
Department of Molecular and Cellular Biology, University of Arizona, 1007 East Lowell Street, Tucson, Arizona 85721, USA.

Abstract

Amino-terminal acetylation is among the most ubiquitous of protein modifications in eukaryotes. Although loss of N-terminal acetylation is associated with many abnormalities, the molecular basis of these effects is known for only a few cases, where acetylation of single factors has been linked to binding avidity or metabolic stability. In contrast, the impact of N-terminal acetylation for the majority of the proteome, and its combinatorial contributions to phenotypes, are unknown. Here, by studying the yeast prion [PSI(+)], an amyloid of the Sup35 protein, we show that loss of N-terminal acetylation promotes general protein misfolding, a redeployment of chaperones to these substrates, and a corresponding stress response. These proteostasis changes, combined with the decreased stability of unacetylated Sup35 amyloid, reduce the size of prion aggregates and reverse their phenotypic consequences. Thus, loss of N-terminal acetylation, and its previously unanticipated role in protein biogenesis, globally resculpts the proteome to create a unique phenotype.

PMID:
25023910
PMCID:
PMC4140192
DOI:
10.1038/ncomms5383
[Indexed for MEDLINE]
Free PMC Article

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