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8.A.165. The Calnexin (Calnexin) Family

The endoplasmic reticulum (ER) is the major folding compartment for secreted and membrane proteins in eukaryotes and is the site of a specific chaperone system, the calnexin cycle, for folding N-glycosylated proteins. Structures of components of the calnexin cycle have revealed quality control mechanisms and protein folding pathways in the ER. In the calnexin cycle, proteins carrying monoglucosylated glycans bind to the lectin chaperones calnexin and calreticulin, which recruit a variety of function-specific chaperones to mediate protein disulfide formation, proline isomerization, and general protein folding. Upon trimming by glucosidase II, the glycan without an inner glucose residue is no longer able to bind to the lectin chaperones. For proteins that have not yet folded properly, the enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) acts as a checkpoint by adding a glucose back to the N-glycan. This allows the misfolded proteins to re-associate with calnexin and calreticulin for additional rounds of chaperone-mediated refolding and prevents them from exiting the ERs. Lee et al. 2020 reviewed progress in structural studies of the calnexin cycle, which revealed common features of how lectin chaperones recruit function-specific chaperones and how UGGT recognizes misfolded proteins. Calnexin aids in the folding of transport proteins (see TC#s 2.A.22.2.10 and 9.A.49.1.2 and 3).

References associated with 8.A.165 family:

Lee, S., Y. Shin, K. Kim, Y. Song, Y. Kim, and S.W. Kang. (2020). Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components. Cells 9:. 32102453