Insight into the Mechanism of SP-B: Investigation of the Lipid-Peptide Interactions of SP-B Fragments

Surfactant protein B (SP-B) is critical to the biophysical activity of pulmonary surfactant and absolutely essential for life. Its molecular mechanism remains unclear in large part because a three dimensional structure remains unattained despite 25 years of research. However, peptide fragments of SP-B have provided some clues about mechanism. Mini-B (SP-B8-25, 63-78) and Super Mini-B (SP-B1-25, 63-78), featuring the amphipathic N- and C-terminal helices of SP-B, have been shown to retain the biophysical activity of the full-length protein in in vivo and in vitro studies. I have used atomistic molecular dynamic simulations with these fragments to provide insight into their mechanisms of lipid interactions and to illuminate important structural features of SP-B. We offer evidence that Mini-B and Super Mini-B promote transitions between lamellar structures and non-lamellar structures via close amphipathic helical interactions. Additionally, we provide evidence that suggests that the N-terminal seven residues of SP-B may enhance the lipid interactions of the N-terminal helix and assume a polyproline II conformation.