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NMR structure of Mini-B, an N-terminal- C-terminal construct from human Surfactant Protein-B (SP-B), in Hexafluoroisopropanol (HFIP)
Structural highlights
DiseasePSPB_HUMAN Defects in SFTPB are the cause of pulmonary surfactant metabolism dysfunction type 1 (SMDP1) [MIM:265120; also called pulmonary alveolar proteinosis due to surfactant protein B deficiency. A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.[1] Genetic variations in SFTPB are a cause of susceptibility to respiratory distress syndrome in premature infants (RDS) [MIM:267450. RDS is a lung disease affecting usually premature newborn infants. It is characterized by deficient gas exchange, diffuse atelectasis, high-permeability lung edema and fibrin-rich alveolar deposits called 'hyaline membranes'. Note=A variation Ile to Thr at position 131 influences the association between specific alleles of SFTPA1 and respiratory distress syndrome in premature infants.[2] FunctionPSPB_HUMAN Pulmonary surfactant-associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-B increases the collapse pressure of palmitic acid to nearly 70 millinewtons per meter. Publication Abstract from PubMedSurfactant protein B (SP-B) is essential for normal lung surfactant function, which is in itself essential to life. However, the molecular basis for SP-B's activity is not understood and a high-resolution structure for SP-B has not been determined. Mini-B is a 34-residue peptide with internal disulfide linkages that is composed of the N- and C-terminal helical regions of SP-B. It has been shown to retain similar activity to full-length SP-B in certain in vitro and in vivo studies. We have used solution NMR to determine the structure of Mini-B in the presence of micelles composed of the anionic detergent sodium dodecyl sulfate (SDS). Under these conditions, Mini-B forms two alpha-helices connected by an unstructured loop. Mini-B possesses a strikingly amphipathic surface with a large positively charged patch on one face of the peptide and a large hydrophobic patch on the opposite face. A tryptophan side chain extends outward from the peptide in a position to interact with lipids at the polar/apolar interface. Interhelix interactions are stabilized by both disulfide bonds and by interleaving of hydrophobic side chains from the two helices. Structure of mini-B, a functional fragment of surfactant protein B, in detergent micelles.,Sarker M, Waring AJ, Walther FJ, Keough KM, Booth V Biochemistry. 2007 Oct 2;46(39):11047-56. Epub 2007 Sep 11. PMID:17845058[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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