Orientation of Bound Ligands in Mannose-binding Proteins IMPLICATIONS FOR MULTIVALENT LIGAND RECOGNITION*

Mannose-binding proteins (MBPs) are C-type animal lectins that recognize high mannose oligosaccharides on pathogenic cell surfaces. MBPs bind to their carbohy-drate ligands by forming a series of Ca2 coordination and hydrogen bonds with two hydroxyl groups equiva-lent to the 3- and 4-OH of mannose. In this work, the determinants of the orientation of sugars bound to rat serum and liver MBPs (MBP-A and MBP-C) have been systematically investigated. The crystal structures of MBP-A soaked with monosaccharides and disaccharides and also the structure of the MBP-A trimer cross-linked by a high mannose asparaginyl oligosaccharide reveal that monosaccharides or 1–6-linked mannose bind to MBP-A in one orientation, whereas 1–2- or 1–3-linked mannose binds in an orientation rotated 180 ° around