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 |
|---|---|
| Pages (from-to) | 651-659 |
| Number of pages | 9 |
| Journal | Traffic |
| Volume | 11 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2010 |
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Keywords
- Disulphide bonds
- Endoplasmic reticulum
- Glycosylation
- Protein folding
- Quality control
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Genetics
- Molecular Biology
- Structural Biology
Cite this
ERp44 and ERGIC-53 synergize in coupling efficiency and fidelity of IgM polymerization and secretion. / Cortini, Margherita; Sitia, Roberto.
In: Traffic, Vol. 11, No. 5, 05.2010, p. 651-659.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - ERp44 and ERGIC-53 synergize in coupling efficiency and fidelity of IgM polymerization and secretion
AU - Cortini, Margherita
AU - Sitia, Roberto
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Disulphide bonds
KW - Endoplasmic reticulum
KW - Glycosylation
KW - Protein folding
KW - Quality control
UR - http://www.scopus.com/inward/record.url?scp=77953148190&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953148190&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0854.2010.01043.x
DO - 10.1111/j.1600-0854.2010.01043.x
M3 - Article
C2 - 20102547
AN - SCOPUS:77953148190
VL - 11
SP - 651
EP - 659
JO - Traffic
JF - Traffic
SN - 1398-9219
IS - 5
ER -