title: A model for the structure and mechanism of action of pulmonary surfactant protein B.
abstract: 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.
authors.affiliation: *Departmento de Bioquímica, Facultad de Biología, Universidad Complutense, Madrid, Spain; and Centro de Astrobiología (INTA-CSIC), Torrejón de Ardoz, Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Olmeda
authors.affiliation: *Departmento de Bioquímica, Facultad de Biología, Universidad Complutense, Madrid, Spain; and Centro de Astrobiología (INTA-CSIC), Torrejón de Ardoz, Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: García-Álvarez
authors.affiliation: *Departmento de Bioquímica, Facultad de Biología, Universidad Complutense, Madrid, Spain; and Centro de Astrobiología (INTA-CSIC), Torrejón de Ardoz, Madrid, Spain.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Gómez
authors.affiliation: *Departmento de Bioquímica, Facultad de Biología, Universidad Complutense, Madrid, Spain; and Centro de Astrobiología (INTA-CSIC), Torrejón de Ardoz, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez-Calle
authors.affiliation: *Departmento de Bioquímica, Facultad de Biología, Universidad Complutense, Madrid, Spain; and Centro de Astrobiología (INTA-CSIC), Torrejón de Ardoz, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cruz
authors.affiliation: *Departmento de Bioquímica, Facultad de Biología, Universidad Complutense, Madrid, Spain; and Centro de Astrobiología (INTA-CSIC), Torrejón de Ardoz, Madrid, Spain jperezgil@bio.ucm.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Gil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002793:Cholic Acids / Q000737:chemistry; D003902:Detergents / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D049231:Saposins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013552:Swine
chemical_list: D002793:Cholic Acids; D003902:Detergents; D008051:Lipid Bilayers; D008563:Membrane Lipids; D037701:Pulmonary Surfactant-Associated Protein B; D049231:Saposins; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate
keywords: air-liquid interface; lipid transport; lipid-protein interaction; lung; saposin