Calnexin cycle – structural features of the ER chaperone system
Citations Over TimeTop 1% of 2020 papers
Abstract
The endoplasmic reticulum (ER) is the major folding compartment for secreted and membrane proteins and is the site of a specific chaperone system, the calnexin cycle, for folding N-glycosylated proteins. Recent structures of components of the calnexin cycle have deepened our understanding of 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. Here, we review progress in structural studies of the calnexin cycle, which reveal common features of how lectin chaperones recruit function-specific chaperones and how UGGT recognizes misfolded proteins.
Related Papers
- → Enhanced Catalysis of Ribonuclease B Folding by the Interaction of Calnexin or Calreticulin with ERp57(1998)334 cited
- → Participation of lectin chaperones and thiol oxidoreductases in protein folding within the endoplasmic reticulum(2010)111 cited
- → Chaperones and foldases in endoplasmic reticulum stress signaling in plants(2011)97 cited
- → ERp57 and PDI: multifunctional protein disulfide isomerases with similar domain architectures but differing substrate–partner associationsThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.(2006)118 cited
- → The low-density lipoprotein receptor-related protein associates with calnexin, calreticulin, and protein disulfide isomerase in receptor-associated-protein-deficient fibroblasts(2003)9 cited