The N-terminal propeptide of lung surfactant protein C is necessary for biosynthesis and prevents unfolding of a metastable alpha-helix.
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.
Li
Jing
J
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Hosia
Waltteri
W
Hamvas
Aaron
A
Thyberg
Johan
J
Jörnvall
Hans
H
Weaver
Timothy E
TE
Johansson
Jan
J
D002942:Circular Dichroism; D041961:Deuterium Exchange Measurement; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D037661:Pulmonary Surfactant-Associated Proteins / Q000737:chemistry / Q000378:metabolism*
D011498:Protein Precursors; D037661:Pulmonary Surfactant-Associated Proteins