A cysteine-rich domain of the “mannose” receptor mediates GalNAc-4-SO4 binding

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-03, Vol.95 (5), p.2089-2093
• Main Authors: Fiete, D J, Beranek, M C, Baenziger, J U
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites; Biological Sciences; Carbohydrate Conformation; Carbohydrate Sequence; CHO Cells; Cricetinae; Kinetics; Lectins, C-Type; Luteinizing Hormone - chemistry; Luteinizing Hormone - metabolism; Mannose Receptor; Mannose-Binding Lectins; Models, Molecular; Molecular Sequence Data; Oligosaccharides - chemistry; Oligosaccharides - metabolism; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.5.2089

A critical element of lutropin bioactivity in vivo is its rapid removal from the blood by a receptor, located in hepatic endothelial cells, that recognizes the terminal sulfated carbohydrate structure SO 4 -4-GalNAcβ1,4GlcNAcβ1,2Manα (S4GGnM). We have previously shown that the macrophage mannose (Man)-receptor cDNA directs the synthesis of a protein that binds oligosaccharides with either terminal S4GGnM or terminal Man, at independent sites. We now show that the cysteine-rich (Cys-Rich) domain at the N terminus of the Man/S4GGnM receptor accounts for binding of oligosaccharides with terminal GalNAc-4-SO 4 , whereas calcium-dependent carbohydrate recognition domains (CRDs) account for binding of ligands containing terminal Man. The Cys-Rich domain is thus a previously unrecognized carbohydrate binding motif. Cys-Rich domains have been described on the three other members of the endocytic C-type lectin family of receptors. The structural relationship of these receptors to the Man/S4GGnM receptor raises the possibility that their Cys-Rich domains also bind carbohydrate moieties and contribute to their function.