Figure 5.

Scheme for a possible mode of cooperative interaction between CRT and ERp57 in assisting the folding of a glycoprotein based on currently available structural, biochemical, and cell-biological data (2, 7, 8). The substrate glycoprotein (blue) binds to the CRT lectin domain (red) by means of a branched oligosaccharide. CRT and CNX both interact specifically with the Glc₁Man₉GlaNAc₂ form of the oligosaccharide (26–28). The interaction of the terminal glucose (light blue circle) with the binding site (white circle) would place the glycoprotein polypeptide chain in the partially solvent-shielded cavity bounded by the CRT lectin domain, the P-domain, and ERp57 (orange) bound to the distal end of the protruding P-domain. It is further hypothesized that the CRT-ERp57 interaction places the thiol-disulfide oxidoreductase favorably for the formation of intermolecular disulfide bonds (S—S) with the glycoprotein.