Surfactant protein B (SP-B), from the saposin-like family of proteins, is essential to facilitate the formation and proper performance of surface active films at the air-liquid interface of mammalian lungs, and lack of or deficiency in this protein is associated with lethal respiratory failure. Despite its importance, neither a structural model nor a molecular mechanism of SP-B is available. The purpose of the present work was to purify and characterize native SP-B supramolecular assemblies to provide a model supporting structure-function features described for SP-B. Purification of porcine SP-B using detergent-solubilized surfactant reveals the presence of 10 nm ring-shaped particles. These rings, observed by atomic force and electron microscopy, would be assembled by oligomerization of SP-B as a multimer of dimers forming a hydrophobically coated ring at the surface of phospholipid membranes or monolayers. Docking of rings from neighboring membranes would lead to formation of SP-B-based hydrophobic tubes, competent to facilitate the rapid flow of surface active lipids both between membranes and between surfactant membranes and the interface. A similar sequential assembly of dimers, supradimeric oligomers and phospholipid-loaded tubes could explain the activity of other saposins with colipase, cytolysin, or antibiotic activities, offering a common framework to understand the range of functions carried out by saposins.
Keywords: air-liquid interface; lipid transport; lipid-protein interaction; lung; saposin.
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