Communication
The N-terminal Propeptide of Lung Surfactant Protein C is Necessary for Biosynthesis and Prevents Unfolding of a Metastable α-Helix

https://doi.org/10.1016/j.jmb.2004.03.051Get rights and content

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.

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Acknowledgements

This work was supported by the Swedish Research Council, Chiesi Farmaceutici, Parma, Italy, the US National Institutes of Health, the Swedish Heart-Lung Foundation, and the King Gustaf V 80th Birthday Fund.

References (33)

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