STRUCTURAL-CHANGES OF SURFACTANT PROTEIN-A INDUCED BY CATIONS REORIENT THE PROTEIN ON LIPID BILAYERS

Surfactant protein A (SP-A) is an octadecameric hydrophilic glycoprote in and is the major protein component of pulmonary surfactant. This pr otein complex plays several roles in the body, such as regulation of s urfactant secretion, recycling and adsorption of surfactant lipids, an d non-serum-induced immune response. Many of SP-A's activities are dep endent upon the presence of cations, especially calcium. Here, we have studied in vitro the effect of cations on the interaction of purified bovine SP-A with phospholipid vesicles made of dipalmitoylphosphatidy lcholine add unsaturated phosphatidylcholine. We have found that SP-A octadecamers exist in an ''opened-bouquet'' conformation in the absenc e of cations and interact with lipid membranes via one or two globular headgroups. Calcium-induced structural changes in SP-A lead to the fo rmation of a clearly identifiable stem in a ''closed-bouquet'' conform ation. This change, in turn, seemingly results in all of SP-A's globul ar headgroups interacting with the lipid membrane surface and with the stem pointing away from the membrane surface. These results represent direct evidence that the headgroups of SP-A (comprising carbohydrate recognition domains), and not the stem (comprising the amino-terminus and collagenlike region), interact with lipid bilayers. Our data suppo rt models of tubular myelin in which the headgroups, not the tails, in teract with the lipid walls of the lattice. (C) 1998 Academic Press.