The x-ray crystal structure of calnexin revealed a globular lectin domain and a long hydrophobic arm extending out. After repeated rounds of calnexin binding, mutant PMP22 is modified by ubiquitin for degradation by the proteasome as well as a Golgi to ER retrieval pathway to return any misfolded PMP22 that escaped from the ER to the Golgi apparatus. This association prepares the MHC class I for binding an antigen for presentation on the cell surface.Ī prolonged association of calnexin with mutant misfolded PMP22 known to cause Charcot-Marie-Tooth Disease leads to the sequestration, degradation and inability of PMP22 to traffic to the Schwann cell surface for myelination. Īfter the β2-microglobulin binds to the MHC class I peptide-loading complex (PLC), calreticulin and ERp57 take over the job of chaperoning the MHC class I protein while the tapasin links the complex to the transporter associated with antigen processing (TAP) complex. As newly synthesized MHC class I α-chains enter the endoplasmic reticulum, calnexin binds on to them retaining them in a partly folded state. Ĭalnexin associates with the protein folding enzyme ERp57 to catalyze glycoprotein specific disulfide bond formation and also functions as a chaperone for the folding of MHC class I α-chain in the membrane of the ER. Yos-9 recognizes mannose residues exposed after α-mannosidase removal of an outer mannose of misfolded glycoproteins. The mannose lectin Yos-9 (OS-9 in humans) marks and sorts misfolded glycoproteins for degradation. The improperly-folded glycoprotein chain thus loiters in the ER and the expression of EDEM/Htm1p which eventually sentences the underperforming glycoprotein to degradation by removing one of the nine mannose residues. If the glycoprotein is not properly folded, an enzyme called UGGT (for UDP-glucose:glycoprotein glucosyltransferase) will add the glucose residue back onto the oligosaccharide thus regenerating the glycoprotein's ability to bind to calnexin. Glucosidase II can also remove the third and last glucose residue. These monoglucosylated oligosaccharides result from the trimming of two glucose residues by the sequential action of two glucosidases, I and II. Ĭalnexin binds only those N- glycoproteins that have GlcNAc2Man9Glc1 oligosaccharides. It specifically acts to retain unfolded or unassembled N-linked glycoproteins in the ER. Function Ĭalnexin is a chaperone, characterized by assisting protein folding and quality control, ensuring that only properly folded and assembled proteins proceed further along the secretory pathway. It consists of a large (50 kDa) N-terminal calcium- binding lumenal domain, a single transmembrane helix and a short (90 residues), acidic cytoplasmic tail. interleukin-35-mediated signaling pathwayĬalnexin (CNX) is a 67kDa integral protein (that appears variously as a 90kDa, 80kDa, or 75kDa band on western blotting depending on the source of the antibody) of the endoplasmic reticulum (ER).interleukin-27-mediated signaling pathway.interleukin-12-mediated signaling pathway.protein folding in endoplasmic reticulum.antigen processing and presentation of peptide antigen via MHC class I.
antigen processing and presentation of exogenous peptide antigen via MHC class II.
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