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Analysis of Protein Folding, Transport, and Degradation in Living Cells by Radioactive Pulse Chase
Published on: February 12, 2019
Glycoprotein folding, quality control and ER-associated degradation
1Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. gerardo@post.tau.ac.il
Current Opinion in Structural Biology
|July 21, 2009
Summary
Misfolded glycoproteins undergo extensive N-glycan trimming in the endoplasmic reticulum (ER) by mannosidase I. This generates specific oligosaccharide structures recognized for degradation, distinct from those guiding properly folded proteins.
Area of Science:
- Glycobiology
- Protein Folding
- Cellular Quality Control
Background:
- Nascent N-linked glycoproteins contain a large Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor.
- Sequential trimming of this precursor generates diverse glycan structures.
- The calnexin folding cycle specifically interacts with monoglucosylated oligosaccharides.
Purpose of the Study:
- To elucidate the trimming code of N-glycans on misfolded glycoproteins.
- To understand the lectin-mediated decoding of these trimmed structures.
- To identify the enzymes involved in N-glycan processing during quality control.
Main Methods:
- Analysis of N-glycan structures on glycoproteins.
- Investigating the role of endoplasmic reticulum (ER) mannosidase I.
- Assessing lectin binding affinities to different glycan structures.
Main Results:
- N-glycans of misfolded glycoproteins are trimmed extensively, removing three to four mannose residues.
- Endoplasmic reticulum (ER) mannosidase I is the primary enzyme responsible for this degradation-focused trimming.
- Shortened glycans (Man(5-6)GlcNAc(2)) are recognized by OS9 for ubiquitination.
- Properly folded glycoproteins bind lectins recognizing Man(8-9)GlcNAc(2) for Golgi transit.
Conclusions:
- N-glycan trimming serves as a critical signal for glycoprotein quality control.
- Distinct glycan structures dictate either degradation or progression through the secretory pathway.
- The OS9 lectin plays a key role in targeting misfolded glycoproteins for degradation via specific glycan recognition.
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