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In this thesis, the lectin site of the molecular chaperone calreticulin is characterized by analyzing key residues required for oligosaccharide binding. Knowledge of the lectin site of calreticulin"s homolog calnexin allowed for the identification of six corresponding calreticulin residues that were then individually mutated. Mutations at four residues completely abolished oligosaccharide binding, suggesting that calreticulin"s lectin site is largely similar to calnexin"s lectin site. Comparison of oligosaccharide-binding deficient mutants to wild type calreticulin with respect to resistance to protease digestion and ability to bind the thiol oxidoreductase ERp57 showed that the mutants were structurally similar to wild type calreticulin. Only oligosaccharide binding was disrupted by the mutations. In vitro aggregation assays determined that the mutants suppressed the aggregation of a non-glycosylated substrate like wild type calreticulin, but were substantially impaired in aggregation suppression of a glycosylated substrate, thus illustrating the importance of the lectin site for interacting with glycosylated substrates.
|The Physical Object|
|Number of Pages||112|
Abstract Calreticulin (CRT) is a soluble molecular chaperone of the endoplasmic reticulum that functions to promote protein folding as well as to retain misfolded proteins. Similar to its membrane-bound paralog calnexin (CNX), CRT is a lectin that preferentially interacts with glycoproteins bearing GlcMan,,GlcNAc2 oligosaccharides. Although the lectin. Calreticulin (CRT) is a soluble molecular chaperone of the endoplasmic reticulum that functions to promote protein folding as well as to retain misfolded proteins. Similar to its membrane-bound paralog calnexin (CNX), CRT is a lectin that preferentially interacts with glycoproteins bearing Glc1Man5–9GlcNAc2 by: Calreticulin is a molecular chaperone of the endoplasmic reticulum that uses both a lectin site specific for Glc(1)Man()GlcNAc(2) oligosaccharides and a polypeptide binding site to interact. Calnexin and calreticulin are related proteins that comprise an ER chaperone system that ensures the proper folding and quality control of newly synthesized glycoproteins. The speciﬁcity for glycoproteins is conferred by a lectin site that recognizes an early oligosaccharide processing intermediate on the folding glycoprotein, Glc 1Man Cited by:
Calnexin and calreticulin are related proteins that comprise an ER chaperone system that ensures the proper folding and quality control of newly synthesized glycoproteins. The specificity for glycoproteins is conferred by a lectin site that recognizes an early oligosaccharide processing intermediate on the folding glycoprotein, Glc1Man9GlcNAc2. In addition, calnexin and calreticulin Cited by: Calreticulin resides in the lumen of the endoplasmic reticulum (ER), where it functions as a molecular chaperone for many glycoproteins, assisting their regular folding. 5 In addition, the C-terminal domain of calreticulin is responsible for calcium-buffering activity, which controls calcium homeostasis and, in turn, signaling processes. Somatic CALR mutations result in insertions and Cited by: 7. In this chapter we present the evidence that calnexin (CNX) and calreticulin (CRT) function as molecular chaperones to assist in the folding and subunit assembly of the majority of Asn-linked Calnexin and Calreticulin, Molecular Chaperones of the Endoplasmic Reticulum | SpringerLinkCited by: 7. Calreticulin is a ubiquitous endoplasmic reticulum Ca 2+ binding chaperone. The protein has been implicated in a variety of diverse functions. Calreticulin is a lectin-like chaperone and, together with calnexin, it plays an important role in quality control during Cited by:
Calnexin (CNX) and calreticulin (CRT) are ER-resident lectin-like molecular chaperones involved in the quality control of secretory or membrane glycoproteins. They can exert molecular chaperone functions via specific binding to the early processing intermediates of Glc 1 Man 9 GlcNAc 2 oligosaccharides of N -glycoproteins. Calnexin and calreticulin are molecular chaperones of the endoplasmic reticulum (ER) whose folding-promoting functions are directed predominantly toward aspargine-linked glycoproteins. Calreticulin is a lectin chaperone of the endoplasmic reticulum that interacts with newly synthesized glycoproteins by binding to Glc 1 Man 9 GlcNAc 2 oligosaccharides as well as to the polypeptide chain. In vitro, the latter interaction potently suppresses the aggregation of various non-glycosylated by: 5. lectin site. Finally, the lectin sites of calnexin and calreticulin were mapped to a region dominated by two sequence motifs that are tmdemly repeated. Similar sequences have not been identified in other lectin families and as a result this segment constitutes a novel lectin : Aikaterini Vassilakos.