Related Experiment Videos
Chaperone selection during glycoprotein translocation into the endoplasmic reticulum
1Swiss Federal Institute of Technology Zurich (ETHZ), Universitätstrasse 16, CH-8092 Zurich, Switzerland.
Science (New York, N.Y.)
|April 15, 2000
Summary
Glycoprotein folding in the endoplasmic reticulum depends on N-linked glycan location. Proximity to the NH2-terminus directs proteins to calnexin/calreticulin, bypassing BiP chaperone. This impacts protein folding pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Newly synthesized proteins in the endoplasmic reticulum require molecular chaperones and folding enzymes for proper folding.
- Glycoproteins can utilize different folding pathways, involving either the BiP chaperone or the calnexin/calreticulin pathway.
Purpose of the Study:
- To investigate the factors determining differential glycoprotein interaction with BiP versus the calnexin/calreticulin pathway.
- To understand the initial chaperone selection mechanism for glycoprotein folding.
Main Methods:
- Studied the folding of Semliki forest virus glycoproteins and influenza hemagglutinin in living cells.
- Analyzed the relationship between N-linked glycan location and chaperone interaction.
Main Results:
- The initial molecular chaperone choice for glycoprotein folding is dictated by the position of N-linked glycans on the nascent polypeptide chain.
- Glycans located within approximately 50 residues of the NH2-terminus promote direct interaction with calnexin and calreticulin, bypassing BiP.
Conclusions:
- N-linked glycan positioning is a critical determinant of glycoprotein folding pathways in the endoplasmic reticulum.
- The calnexin/calreticulin pathway is preferentially engaged for proteins with N-linked glycans near their N-terminus.