Transient, lectin-like association of calreticulin with folding intermediates of cellular and viral glycoproteins

Jeffrey R. Peterson, Ari Ora, Phuc Nguyen Van, Ari Helenius*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

262 Citations (Scopus)

Abstract

The soluble, calcium-binding protein calreticulin shares high sequence homology with calnexin, a transmembrane chaperone of glycoprotein folding. Our experiments demonstrated that calreticulin, like calnexin, associated transiently with numerous newly synthesized proteins in the endoplasmic reticulum. The population of proteins that bound to calreticulin was partially overlapping with those that bound to calnexin. Hemagglutinin (HA) of influenza virus was shown to associate with both calreticulin and calnexin. Using HA as a model substrate, it was found that both calreticulin- and calnexin-bound HA corresponded primarily to incompletely disulfide- bonded folding intermediates and conformationally trapped forms. Binding of all substrates was oligosaccharide-dependent and required the trimming of glucose residues from asparagine-linked core glycans by glucosidases I and II. In vitro, α-mannosidase digestion of calreticulin-bound HA indicated that calreticulin was specific for monoglucosylated glycans. Thus, calreticulin appeared to be a lectin with similar oligosaccharide specificity as its membrane-bound homologue, calnexin. Both are therefore likely to play an important role in glycoprotein maturation and quality control in the endoplasmic reticulum.

Original languageEnglish
Pages (from-to)1173-1184
Number of pages12
JournalMOLECULAR BIOLOGY OF THE CELL
Volume6
Issue number9
DOIs
Publication statusPublished - 1 Jan 1995
MoE publication typeA1 Journal article-refereed

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