Pulmonary surfactant is essential for respiration and lung host defence and is composed of 80–90% lipids, mainly dipalmitoylphosphatidylcholine (DPPC). Surfactant protein C (SP-C) constitutes 1–2 % of the surfactant mass, and is one of the most hydrophobic peptides yet isolated. SP-C residues 9–34 form an α-helix with a central poly-valine segment, which perfectly matches the thickness of a fluid DPPC bilayer. The palmitoyl groups linked to Cys-5 and Cys-6 of SP-C increase the capacity of the peptide to promote lipid adsorption at an air/liquid interface, and augment the mechanical stability of SP-C/lipid mixtures. SP-C undergoes α-helix → β-sheet transition and forms amyloid fibrils. NMR and MS studies show that the poly-valine helix is kinetically stabilized, and that once it unfolds, formation of β-sheet aggregates is significantly faster than refolding. α-Helix unfolding is accelerated after removal of the palmitoyl groups. Secondary structure prediction of SP-C yields β-strand conformation of the poly-valine part. A database search revealed similar discordance between experimentally determined helices and predicted β-strands for other amyloid-forming proteins, including the prion protein associated with spongiform encephalopathies, and the amyloid-β (Aβ) peptide associated with Alzheimer's disease. For Aβ and SP-C, removal of the helix/strand discordance by residue replacements abrogates fibril formation in vitro.

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