The N-terminal propeptide of lung surfactant protein C is necessary for biosynthesis and prevents unfolding of a metastable alpha-helix

J Mol Biol. 2004 May 14;338(5):857-62. doi: 10.1016/j.jmb.2004.03.051.


The lung surfactant-associated protein C (SP-C) consists mainly of a polyvaline alpha-helix, which is stable in a lipid membrane. However, in agreement with the predicted beta-strand conformation of a polyvaline segment, helical SP-C unfolds and transforms into beta-sheet aggregates and amyloid fibrils within a few days in aqueous organic solvents. SP-C fibril formation and aggregation have been associated with lung disease. Here, we show that in a recently isolated biosynthetic precursor of SP-C (SP-Ci), a 12 residue N-terminal propeptide locks the metastable polyvaline part in a helical conformation. The SP-Ci helix does not aggregate or unfold during several weeks of incubation, as judged by hydrogen/deuterium exchange and mass spectrometry. Hydrogen/deuterium exchange experiments further indicate that the propeptide reduces exchange in parts corresponding to mature SP-C. Finally, in an acidic environment, SP-Ci unfolds and aggregates into amyloid fibrils like SP-C. These data suggest a direct role of the N-terminal propeptide in SP-C biosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • Deuterium Exchange Measurement
  • Protein Precursors / chemistry
  • Protein Precursors / metabolism*
  • Protein Structure, Secondary
  • Pulmonary Surfactant-Associated Proteins / chemistry
  • Pulmonary Surfactant-Associated Proteins / metabolism*


  • Protein Precursors
  • Pulmonary Surfactant-Associated Proteins