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

Jing Li, Waltteri Hosia, Aaron Hamvas, Johan Thyberg, Hans Jörnvall, Timothy E. Weaver, Jan Johansson*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The lung surfactant-associated protein C (SP-C) consists mainly of a polyvaline α-helix, which is stable in a lipid membrane. However, in agreement with the predicted β-strand conformation of a polyvaline segment, helical SP-C unfolds and transforms into β-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.

Original languageEnglish (US)
Pages (from-to)857-862
Number of pages6
JournalJournal of Molecular Biology
Volume338
Issue number5
DOIs
StatePublished - May 14 2004

Keywords

  • Amyloid fibril
  • HDX, hydrogen/deuterium exchange
  • Hydrogen/deuterium exchange
  • Lung disease
  • MALDI, matrix-assisted laser desorption/ionisation
  • Protein aggregation
  • SP, surfactant protein
  • Structural conversion

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'The N-terminal propeptide of lung surfactant protein C is necessary for biosynthesis and prevents unfolding of a metastable α-helix'. Together they form a unique fingerprint.

  • Cite this