Palmitoylation as a Key Factor to Understand Sp-C-Lipid Interactions in the Lung Surfactant System

Abstract

Surfactant protein C (SP-C) has been regarded as the most specific protein linked to lung development. So far, great efforts have been done to understand the structure-function relationships of this lipopeptide, nevertheless its high hydrophobicity and tendency to aggregate forming amyloid-like structures have made its study a challenging task. Previous evidence has pointed out the importance of SP-C palmitoylation in sustaining the proper dynamics of lung surfactant, but the mechanism by which this posttranslational modification stabilizes the interfacial surfactant film under dynamic compression-expansion cycles mimicking the process of breathing, is still unrevealed. In this work we have compared the behavior of a native palmitoylated SP-C with a non-palmitoylated recombinant SP-C (rSP-C) in membrane environments by means of ATR-FTIR spectroscopy. Our results suggest that palmitoylation modulates SP-C-lipid interactions and besides, it may play a dual role in combination with electrostatic interactions with anionic phospholipids (POPG) to maintain a proper SP-C conformation in the lung surfactant context. Functional approaches will provide further insights into SP-C palmitoylation-induced effects, allowing the characterization of SP-C structure-function determinants.