IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5383.html
   My bibliography  Save this article

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

Author

Listed:
  • William M. Holmes

    (Cell Biology and Biochemistry, Brown University
    Present address: Biology Department, College of the Holy Cross, 1 College Street, Worcester, Massachusetts 01610, USA)

  • Brian K. Mannakee

    (Graduate Interdisciplinary Program in Statistics, University of Arizona)

  • Ryan N. Gutenkunst

    (University of Arizona)

  • Tricia R. Serio

    (Cell Biology and Biochemistry, Brown University
    Present address: 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.

Suggested Citation

  • William M. Holmes & Brian K. Mannakee & Ryan N. Gutenkunst & Tricia R. Serio, 2014. "Loss of amino-terminal acetylation suppresses a prion phenotype by modulating global protein folding," Nature Communications, Nature, vol. 5(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5383
    DOI: 10.1038/ncomms5383
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5383
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5383?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Ulises H. Guzman & Henriette Aksnes & Rasmus Ree & Nicolai Krogh & Magnus E. Jakobsson & Lars J. Jensen & Thomas Arnesen & Jesper V. Olsen, 2023. "Loss of N-terminal acetyltransferase A activity induces thermally unstable ribosomal proteins and increases their turnover in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5383. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.