Independent and cooperative roles of N-glycans and molecular chaperones in the folding and disulfide bond formation of the low-density lipoprotein (LDL) receptor-related protein

Lynn M. McCormick, Reiko Urade, Yukino Arakaki, Alan L. Schwartz, Guojun D Bu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The low-density lipoprotein receptor-related protein (LRP) is a large receptor that contains extensive glycosylation sites and disulfide bonds. Here we analyzed how N-linked glycosylation and molecular chaperones function during LRP folding. Treatment of cells with a glycosylation inhibitor tunicamycin significantly impaired LRP folding, although binding to receptor-associated protein (RAP), a specialized chaperone for LRP, was not affected. The effects of tunicamycin on LRP folding were not due to an inhibition of RAP glycosylation since a mutant RAP that harbors a mutation at its sole glycosylation site was still capable of promoting LRP folding. The roles of N-linked glycosylation and the lectin chaperone, calnexin, in LRP folding were further dissected using LRP minireceptors that carry mutations at individual glycosylation sites. Interestingly, we found that RAP interacts with oxidoreductase ERp57 and mediates its interaction with LRP. Since previous studies have shown that N-glycan-bound calnexin/calreticulin are also capable of recruiting ERp57, our results suggest that N-linked glycosylation and RAP can independently and cooperatively recruit oxidoreductases to facilitate protein folding and proper disulfide bond formation.

Original languageEnglish (US)
Pages (from-to)5794-5803
Number of pages10
JournalBiochemistry
Volume44
Issue number15
DOIs
StatePublished - Apr 19 2005
Externally publishedYes

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LDL-Receptor Related Proteins
Lipoprotein Receptors
Molecular Chaperones
Glycosylation
LDL Receptors
Disulfides
Polysaccharides
Protein folding
Protein Folding
Proteins
Calnexin
Tunicamycin
Oxidoreductases
Calreticulin
Mutation
Lectins
Ports and harbors
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Independent and cooperative roles of N-glycans and molecular chaperones in the folding and disulfide bond formation of the low-density lipoprotein (LDL) receptor-related protein. / McCormick, Lynn M.; Urade, Reiko; Arakaki, Yukino; Schwartz, Alan L.; Bu, Guojun D.

In: Biochemistry, Vol. 44, No. 15, 19.04.2005, p. 5794-5803.

Research output: Contribution to journalArticle

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