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N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum

Gabriella M A Forte1, Martin R Pool, Colin J Stirling

  • 1Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.

Plos Biology
|June 10, 2011
PubMed

Insights

N-terminal acetylation, a common protein modification, dictates protein sorting. This study reveals it directs proteins to the cytosol or secretory pathway, impacting cellular sorting conserved across species.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Amino-terminal acetylation is a prevalent post-translational modification in eukaryotes, affecting 50%-80% of proteins.
  • This modification plays a crucial role in various cellular processes, including protein stability and function.

Purpose of the Study:

  • To systematically analyze the N-terminal processing of cytosolic versus secretory pathway proteins.
  • To investigate the impact of N-terminal acetylation on protein sorting and cellular localization.

Main Methods:

  • Bioinformatic analysis of predicted N-terminal sequences of cytosolic and secretory proteins.
  • Investigating the effects of mutations in signal sequences on acetylation and protein sorting.

Main Results:

  • Cytosolic proteins show a strong bias towards N-terminal acetylation, while secretory proteins exhibit a bias against it.
  • Mutations enabling acetylation of secretory signal sequences caused mis-sorting to the cytosol.
  • This mis-sorting was dependent on the N-terminal processing machinery.

Conclusions:

  • N-terminal acetylation is an early, critical determinant of nascent polypeptide sorting to either the cytosol or the secretory pathway.
  • This regulatory mechanism is conserved across a wide range of species, highlighting its fundamental importance in cellular organization.

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