Structure of mini-B, a functional fragment of surfactant protein B, in detergent micelles.
Surfactant 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.
Sarker
Muzaddid
M
Department of Physics & Physical Oceanography, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Waring
Alan J
AJ
Walther
Frans J
FJ
Keough
Kevin M W
KM
Booth
Valerie
V
D000595:Amino Acid Sequence; D003902:Detergents / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
D003902:Detergents; D008823:Micelles; D010446:Peptide Fragments; D037701:Pulmonary Surfactant-Associated Protein B; D012967:Sodium Dodecyl Sulfate