title: Palmitoylation as a key factor to modulate SP-C-lipid interactions in lung surfactant membrane multilayers.
abstract: Surfactant protein C (SP-C) has been regarded as the most specific protein linked to development of mammalian lungs, and great efforts have been done to understand its structure-function relationships. Previous evidence has outlined the importance of SP-C palmitoylation to sustain the proper dynamics of lung surfactant, but the mechanism by which this posttranslational modification aids SP-C to stabilize the interfacial surfactant film along the compression-expansion breathing cycles, is still unrevealed. In this work we have compared the structure, orientation and lipid-protein interactions of a native palmitoylated SP-C with those of a non-palmitoylated recombinant SP-C (rSP-C) form in air-exposed multilayer membrane environments, by means of ATR-FTIR spectroscopy. Palmitoylation does not affect the secondary structure of the protein, which exhibits a full α-helical conformation in partly dehydrated phospholipid multilayer films. However, differences between the Amide I band of the IR spectrum of palmitoylated and non-palmitoylated proteins suggest subtle differences affecting the environment of their helical component. These differences are accompanied by differential effects on the IR bands from phospholipid phosphates, indicating that palmitoylation modulates lipid-protein interactions at the headgroup region of phospholipid layers. On the other hand, the relative dichroic absorption of polarized IR has allowed calculating that the palmitoylated protein adopts a more tilted transmembrane orientation than the non-palmitoylated SP-C, likely contributing to more compact, dehydrated and possibly stable multilayer lipid-protein films. As a whole, the behavior of multilayer films containing palmitoylated SP-C may reflect favorable structural properties for surfactant reservoirs at the air-liquid respiratory interface.
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Biological Sciences, Universidad Complutense de Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Roldan
authors.affiliation: Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles (ULB), Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Goormaghtigh
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Biological Sciences, Universidad Complutense de Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Gil
authors.affiliation: Department of Biochemistry and Molecular Biology I, Faculty of Biological Sciences, Universidad Complutense de Madrid, Spain. Electronic address: bego.garcia.alvarez@gmail.com.
authors.forename: Begoña
authors.initials: B
authors.lastname: Garcia-Alvarez
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D054878:Lipoylation; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D008566:Membranes / Q000737:chemistry* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry* / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013499:Surface Properties; D013552:Swine; D013696:Temperature
chemical_list: D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: ATR-FTIR; Lung surfactant; Palmitoylation; Protein–lipid interaction; SP-C