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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Holmes WM,Mannakee BK,Gutenkunst RN,Serio TR

doi

10.1038/ncomms5383

subject

Has Abstract

pub_date

2014-07-15 00:00:00

pages

4383

issn

2041-1723

pii

ncomms5383

journal_volume

5

pub_type

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