title: 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.
abstract: 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 structure, mapping mostly to the ligand-binding site. It reveals the presence of two calcium ion-binding sites located 6A apart, one of which has no equivalent in the plant lectins. The second metal ion-binding site present in that class of lectins, binding Mn(2+), 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-mannose Man(8)(GlcNAc)(2) glycan common to glycoproteins at the ER exit stage.
authors.affiliation: Molecular Structural Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Velloso
authors.forename: Kerstin
authors.initials: K
authors.lastname: Svensson
authors.forename: Ralf F
authors.initials: RF
authors.lastname: Pettersson
authors.forename: Ylva
authors.initials: Y
authors.lastname: Lindqvist
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D018360:Crystallography, X-Ray; D037241:Mannose-Binding Lectins / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D008670:Metals; D002118:Calcium