Mapping Degradation Signals and Pathways in a Eukaryotic N-terminome

Area of Science:

• Molecular Biology
• Proteomics
• Biochemistry

Background:

• Eukaryotic proteins commonly undergo N-terminal acetylation.
• N-terminal sequences can signal protein degradation via N-end rule pathways.
• The prevalence and specificity of these N-terminal degrons remain largely unknown.

Purpose of the Study:

• To comprehensively survey N-terminal degrons in the yeast proteome.
• To investigate the role of N-terminal sequences and acetylation in protein turnover.
• To identify the features and E3 ubiquitin ligases involved in N-terminal degradation.

Main Methods:

• Systematic examination of protein turnover rates based on N-terminal sequences in yeast.
• Analysis of N-terminal sequences to identify potential degrons.
• Investigation of the interaction between N-terminal features and E3 ubiquitin ligases (Doa10, Ubr1).

Main Results:

• Approximately 26% of nascent yeast proteins contain cryptic N-terminal degrons.
• These degrons are characterized by high hydrophobicity and are recognized by the E3 ubiquitin ligase Doa10, indicating a role in protein quality control.
• N-terminal acetylation infrequently functions as a degron and can, in some cases, block degradation mediated by the E3 ubiquitin ligase Ubr1.

Conclusions:

• Hydrophobicity, rather than N-terminal acetylation, is the primary determinant of N-terminal degrons in nascent proteins.
• N-terminal acetylation exhibits complex roles, sometimes preventing degradation.
• This study reveals the intricate nature of N-terminal regulation of protein stability and quality control.