Abstract
Owing to the quality control mechanisms operating in the early secretory compartment, only native proteins are secreted. Despite the difficulties in assembling planar immunoglobulin M (IgM) polymers, antibody-secreting cells can release up to thousands of IgM per second. The finding that secretory μ (μs) chains bind to ERGIC-53, a lectin transporter that cycles in the early secretory compartment, suggested that ERGIC-53 hexamers could provide a polymerization platform. Here, we show that ERGIC-53 binds to the conserved Asn563 glycan in the C-terminal μs tailpiece (μstp). Removal of this glycan inhibits ERGIC-53 binding and results in the rapid formation of larger polymeric assemblies. In contrast, removal of the Asn402 oligosaccharides prevents both polymerization and secretion. ERp44, a chaperone that interacts with ERGIC-53, binds to Cys575 in the μstp, providing a fail-safe mechanism that retrieves unpolymerized IgM subunits and promotes polymerization. The coordinated action of ERGIC-53 and ERp44 provides a way to improve the efficiency of IgM secretion without perturbing its fidelity.
Original language | English |
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Pages (from-to) | 651-659 |
Number of pages | 9 |
Journal | Traffic |
Volume | 11 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2010 |
Keywords
- Disulphide bonds
- Endoplasmic reticulum
- Glycosylation
- Protein folding
- Quality control
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Genetics
- Molecular Biology
- Structural Biology