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Carbohydrate- and conformation-dependent cargo capture for ER-exit.
Christian Appenzeller-Herzog1, Beat Nyfeler, Peter Burkhard
1Department of Pharmacology and Neurobiology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Molecular Biology of the Cell
|January 7, 2005
Summary
Researchers discovered a novel ER-exit signal in secretory proteins, involving a specific oligosaccharide and beta-hairpin loop. This motif facilitates ER export via the lectin ERGIC-53, acting as a crucial quality control mechanism.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Secretory proteins exit the endoplasmic reticulum (ER) via receptor-mediated mechanisms.
- The specific signals guiding cargo-receptor interactions for ER export remain largely undefined.
Purpose of the Study:
- To identify and characterize novel targeting motifs involved in ER export.
- To elucidate the mechanism of lectin ERGIC-53-assisted export of lysosomal enzymes.
Main Methods:
- Analysis of protein structure and oligosaccharide interactions.
- Investigating the role of specific motifs in protein trafficking.
Main Results:
- A novel ER-export signal, comprising a high-mannose oligosaccharide and a beta-hairpin loop, was identified.
- This motif mediates ER-ERGIC-53-assisted export of procathepsin Z, demonstrating ERGIC-53's lectin selectivity.
- The motif is present in fully folded proteins, indicating a role in ER quality control.
Conclusions:
- A conformation-dependent motif involving oligosaccharides and peptide structure serves as an ER-exit signal for soluble cargo.
- This mechanism, exemplified by procathepsin Z and cathepsin C, represents a quality control system complementing protein folding in the ER.
- This study provides the first documentation of an ER-exit signal in soluble cargo recognized by a transport receptor.