However, recent structural and biochemical data have provided important new insights into this chaperone system and present a solid basis for further mechanistic studies. Role for N-glycans and calnexin-calreticulin chaperones in SARS-CoV-2 Spike maturation and viral infectivity. Compared to other important chaperone systems, such as the Hsp70s, Hsp90s and GroEL/GroES, the principles whereby this system works at the molecular level are relatively poorly understood. The significance of this system is underscored by the fact that CNX and CRT interact with practically all glycoproteins investigated to date, and by the debilitating phenotypes revealed in knockout mice deficient in either gene. Essential components of this system include the lectin chaperones calnexin (CNX) and calreticulin (CRT) and their associated co-chaperone ERp57, a glycoprotein specific thiol-disulfide oxidoreductase. For glycoproteins, the ER possesses a dedicated maturation system, which assists folding and ensures the quality of final products before ER release. It has an 89-residue cytoplasmic tail that is phosphorylated and carries a C-terminal RKPRRE sequence that serves as an ER-localization signalz. ![]() Calreticulin but not calnexin posttranslationally binds to the soluble and heavily glycosylated blood coagulation factor V 47. Calnexin and calreticulin are lectins Calnexin is a nonglycosylated type I membrane protein (65 kDa, 573 amino acids) with its substrate- binding domain in the lumen of the ER. In eukaryotic cells, the endoplasmic reticulum (ER) plays an essential role in the synthesis and maturation of a variety of important secretory and membrane proteins. In general, calnexin binds membrane proximal glycans and calreticulin binds glycans that cannot be reached by calnexin since they emerge deeper into the ER lumen.
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