Membrane properties and amyloid fibril formation of lung surfactant protein C.
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 alpha-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 alpha-helix-->beta-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 beta-sheet aggregates is significantly faster than refolding. alpha-Helix unfolding is accelerated after removal of the palmitoyl groups. Secondary structure prediction of SP-C yields beta-strand conformation of the poly-valine part. A database search revealed similar discordance between experimentally determined helices and predicted beta-strands for other amyloid-forming proteins, including the prion protein associated with spongiform encephalopathies, and the amyloid-beta (Abeta) peptide associated with Alzheimer's disease. For Abeta and SP-C, removal of the helix/strand discordance by residue replacements abrogates fibril formation in vitro.
Johansson
J
J
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden. jan.johansson@mbb.ki.se
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis / Q000737:chemistry*; D000818:Animals; D008565:Membrane Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000737:chemistry* / Q000502:physiology; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000502:physiology
D000682:Amyloid; D008565:Membrane Proteins; D011510:Proteolipids; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine