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A model for the structure and mechanism of action of pulmonary surfactant protein B Olmeda Lozano, Bárbara García Álvarez, María Begoña Gómez, Manuel J. Martínez Calle, Marta Cruz Rodríguez, Antonio Pérez Gil, Jesús 577.2 Saposin Air-liquid interface Lipid transport Lung Lipid-protein interaction Biología Biología molecular (Biología) Bioquímica (Biología) 24 Ciencias de la Vida 2415 Biología Molecular 2302 Bioquímica 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 structuralmodel nor amolecular 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 detergentsolubilized surfactant reveals the presence of 10 nm ringshaped 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. —Olmeda, B., García-Álvarez, B., Gómez, M. J., Martínez-Calle, M., Cruz, A., Perez-Gil, J. A model for the structure and mechanism of action of pulmonary surfactant protein B. FASEB J. 29, 4236–4247 (2015). www.fasebj.org Ministerio de Economía y Competitividad (España) Comunidad de Madrid Sección Deptal. de Bioquímica y Biología Molecular (Biológicas) Fac. de Ciencias Biológicas TRUE pub 2023-06-19T15:10:41Z 2023-06-19T15:10:41Z 2015 journal article https://hdl.handle.net/20.500.14352/35489 0892-6638 10.1096/fj.15-273458 eng BIO2012-30733 (S2013/MlT-2807) restricted access application/pdf Federation of American Societies for Experimental Biology (FASEB)