The Human Mannose-binding Protein Gene

The human mannose-binding protein (MBP)' is an acute phase serum protein of -300 kD comprised of multimers of a 32-kD subunit (1-3). It is a member of an ever-growing family of animal lectins that share at least 18 invariant residues in their carbohydrate recognition domain (CRD). The family can be divided into membrane proteins and soluble proteins, and all bind ligands optimally at neutral pH in the presence of calcium (reviewed in reference 4). For membrane proteins, theCRD is attached to amembrane anchor domain as found in the asialoglycoprotein receptors of rat (5) and human (6, 7), the chicken hepatic lectin (8), the lymphocyte IgE Fc receptor (9), and a rat Kupffer cell-binding protein (10) . This group has recently been expanded to include a lymphocyte homing receptor (11), a granular membrane protein of platelets and endothelium, GMP-140 (12), and ELAM-1, a cytokine-inducible endothelial cell receptor (13) . Thefunction ofthe attachment domains of the soluble lectins, which include MBP (14, 15), the apoprotein of pulmonary surfactant SP-A (16, 17), cartilage proteoglycan core protein (18), a fly (19) and sea urchin lectin (20), and an acorn barnacle lectin (21) are not known_ Only in the rat and human MBP, and dog, human, and rabbit (22) surfactant A protein, are the noncarbohydrate recognition domains similar. In these proteins there is a collagen-like region that is preceded by a cysteine-rich NH2-terminal region that mediates interchain disulphide bonds. As our knowledge of the function of MBP and surfactant Aprotein expands, it appears that each domain of these proteins may have a defined purpose. Until recently, the function of MBP was not known. However, a function in host defense is suggested by its ability to bind yeast manvans (1) and interact with the complement cascade (23), and by our finding that MBP prevents infection of H9 lymphoblasts by HIV by binding to the high mannose glycans expressed on the