The crystal structure of the carbohydrate-recognition domain of the glycoprotein sorting receptor p58/ERGIC-53 reveals an unpredicted metal-binding site and conformational changes associated with calcium ion binding

p58/ERGIC-53 is a calcium-dependent animal lectin that acts as a cargo. receptor, binding to a set of glycoproteins in the endoplasmic reticulum (ER) and transporting them to the Golgi complex. It is similar in structure to calcium-dependent leguminous lectins. We have determined the structure of the carbohydrate-recognition domain of p58/ERGIC-53 in its calcium-bound form. The structure reveals localized but large conformational changes in relation to the previously determined metal ion-free 1 structure, mapping mostly to the ligand-binding site. It reveals the presence of two calcium ion-binding sites located 6 Angstrom apart, one of which has no equivalent in the plant lectins. The second metal ion-binding site present in that class of lectins, binding Mn2+, is absent from p58/ERGIC-53. The absence of a short loop in the ligand-binding site in this protein suggests that it has adapted to optimally bind the high-marmose Man(8)(GIcNAc)(2) glycan common to glycoproteins at the ER exit stage. (C) 2003 Elsevier Ltd. All rights reserved.