O-mannosylation of misfolded ER proteins promotes ERAD
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View abstract on PubMed
Summary
This summary is machine-generated.Protein quality control involves endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins. This study reveals Pbn1-Gpi14
Area Of Science
- Molecular Biology
- Cell Biology
- Biochemistry
Background
- Protein quality control (PQC) in the secretory pathway is crucial for cellular health and linked to human diseases.
- Endoplasmic reticulum-associated degradation (ERAD) targets terminally misfolded proteins for degradation.
- The Pbn1-Gpi14 complex is known as a GPI-mannosyltransferase.
Purpose Of The Study
- To investigate the degradation mechanisms of misfolded proteins, specifically Gas1*, in Saccharomyces cerevisiae.
- To uncover novel functions of the Pbn1-Gpi14 complex in protein quality control.
- To explore the role of protein O-mannosylation in ERAD.
Main Methods
- Genome-wide screens in baker's yeast (Saccharomyces cerevisiae).
- Biochemical analyses of protein degradation pathways.
- Genetic analyses to identify key factors in ERAD.
Main Results
- The Pbn1-Gpi14 complex exhibits bifunctionality, acting as both a GPI-mannosyltransferase and a catalyst for O-mannosylation of misfolded proteins.
- O-mannosylation by Pbn1-Gpi14 promotes ERAD of misfolded proteins, especially those lacking N-glycans.
- This identifies a novel glycan-dependent mechanism for promoting ERAD.
Conclusions
- Protein O-mannosylation is a newly discovered mechanism that promotes the ER-associated degradation of misfolded proteins.
- The Pbn1-Gpi14 complex plays a critical, previously unrecognized role in targeting misfolded proteins for degradation via O-mannosylation.
- This finding expands our understanding of protein quality control pathways and their implications for human diseases.
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