title: Structure-function correlations of pulmonary surfactant protein SP-B and the saposin-like family of proteins.
abstract: Pulmonary surfactant is a lipid-protein complex secreted by the respiratory epithelium of mammalian lungs, which plays an essential role in stabilising the alveolar surface and so reducing the work of breathing. The surfactant protein SP-B is part of this complex, and is strictly required for the assembly of pulmonary surfactant and its extracellular development to form stable surface-active films at the air-liquid alveolar interface, making the lack of SP-B incompatible with life. In spite of its physiological importance, a model for the structure and the mechanism of action of SP-B is still needed. The sequence of SP-B is homologous to that of the saposin-like family of proteins, which are membrane-interacting polypeptides with apparently diverging activities, from the co-lipase action of saposins to facilitate the degradation of sphingolipids in the lysosomes to the cytolytic actions of some antibiotic proteins, such as NK-lysin and granulysin or the amoebapore of Entamoeba histolytica. Numerous studies on the interactions of these proteins with membranes have still not explained how a similar sequence and a potentially related fold can sustain such apparently different activities. In the present review, we have summarised the most relevant features of the structure, lipid-protein and protein-protein interactions of SP-B and the saposin-like family of proteins, as a basis to propose an integrated model and a common mechanistic framework of the apparent functional versatility of the saposin fold.
authors.affiliation: Departamento de Bioquimica, Facultad de Biologia, Universidad Complutense, Jose Antonio Novais 2, 28040, Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Olmeda
authors.forename: Begoña
authors.initials: B
authors.lastname: García-Álvarez
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Gil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry* / Q000378:metabolism*; D049231:Saposins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D037701:Pulmonary Surfactant-Associated Protein B; D049231:Saposins