title: Crystal structure of the carbohydrate recognition domain of p58/ERGIC-53, a protein involved in glycoprotein export from the endoplasmic reticulum.
abstract: p58/ERGIC-53 is an animal calcium-dependent lectin that cycles between the endoplasmic reticulum (ER) and the Golgi complex and appears to act as a cargo receptor for a subset of soluble glycoproteins exported from the ER. We have determined the crystal structure of the carbohydrate recognition domain (CRD) of p58, the rat homologue of human ERGIC-53, to 1.46 A resolution. The fold and ligand binding site are most similar to those of leguminous lectins. The structure also resembles that of the CRD of the ER folding chaperone calnexin and the neurexins, a family of non-lectin proteins expressed on neurons. The CRD comprises one concave and one convex beta-sheet packed into a beta-sandwich. The ligand binding site resides in a negatively charged cleft formed by conserved residues. A large surface patch of conserved residues with a putative role in protein-protein interactions and oligomerization lies on the opposite side of the ligand binding site. Together with previous functional data, the structure defines a new and expanding class of calcium-dependent animal lectins and provides a starting point for the understanding of glycoprotein sorting between the ER and the Golgi.
authors.affiliation: Division of Molecular Structural Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Tomtebodavägen 6, S-17177 Stockholm, Sweden.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Velloso
authors.forename: Kerstin
authors.initials: K
authors.lastname: Svensson
authors.forename: Gunter
authors.initials: G
authors.lastname: Schneider
authors.forename: Ralf F
authors.initials: RF
authors.lastname: Pettersson
authors.forename: Ylva
authors.initials: Y
authors.lastname: Lindqvist
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D011487:Protein Conformation; D021381:Protein Transport; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013499:Surface Properties
chemical_list: D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D037102:Lectins; D008024:Ligands; C501458:Lman1 protein, rat; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D037281:Calnexin