Interaction of the N-terminal segment of pulmonary surfactant protein SP-C with interfacial phospholipid films

Abstract

Pulmonary surfactant protein SP-C is a 35-residue polypeptide composed of a hydrophobic transmembrane alpha-helix and a polycationic, palmitoylated-cysteine containing N-terminal segment. This segment is likely the only structural motif the protein projects out of the bilayer in which SP-C is inserted and is therefore a candidate motif to participate in interactions with other bilayers or monolayers. In the present work, we have detected intrinsic ability of a peptide based on the sequence of the N-terminal segment of SP-C to interact and insert spontaneously into preformed zwitterionic or anionic phospholipid monolayers. The peptide expands the pi-A compression isotherms of interfacial phospholipid/peptide films, and perturbs the lipid packing of phospholipid films during compression-driven liquid-expanded to liquid-condensed lateral transitions, as observed by epifluorescence microscopy. These results demonstrate that the sequence of the SP-C N-terminal region has intrinsic ability to interact with, insert into, and perturb the structure of zwitterionic and anionic phospholipid films, even in the absence of the palmitic chains attached to this segment in the native protein. This effect has been related with the ability of SP-C to facilitate reinsertion of surface active lipid molecules into the lung interface during respiratory compression-expansion cycling.

Protein–lipid interactions and surface activity in the pulmonary surfactant system

“…Changes in the surface area permit to mimic the compression-expansion cycles of breathing but in a relatively static way that does not reflect the dynamic process of breathing. One of the most important advantages of this technique is that radiography and epifluorescence microscopy of the surface film can be easily performed using labeled proteins or lipids (Nag et al, 1997;Plasencia et al, 2005;Yan et al, 2005). This enables visualization of lipid and lipid-protein domains as well as the study of the lateral distribution of the membrane-associated proteins at the air-liquid interface.…”

“…More recently the study of the N-terminal segment of the protein has been addressed using synthetic peptides based in the sequence of this region of the lipopeptide (Plasencia et al, 2001(Plasencia et al, , 2004(Plasencia et al, , 2005Bi et al, 2002). These peptides from the N-terminal tail of SP-C seem to adopt an amphipathic conformation, with strong tendency to partition into the interface of phospholipid membranes and monolayers, even in the absence of palmitoylated cysteines (Plasencia et al, 2004(Plasencia et al, , 2005. The interaction of this region with membranes produces perturbations of the lipid packing, with consequences in membrane permeability.…”

Synthetic Pulmonary Surfactant Preparations: New Developments and Future Trends

“…Recent studies using short synthetic peptides derived from the Nterminal region of SP-C demonstrate that this region has a high affinity toward membrane interfaces, even in the absence of palmitoylated cysteines, and is able to produce perturbations in lipid packing and membrane permeability in surfactant membranes [144] and interfacial films [145]. It is, therefore, proposed that the N-terminal region could play a major role in the ability of SP-C to promote interfacial adsorption of phospholipids.…”

Comparative analysis of new peptide conjugates of antitubercular drug candidates—Model membrane and in vitro studies

“…Simplified lipid model systems were applied to study the details of membrane affinity of the bioactive compounds. The Langmuir monolayer of lipid molecules is a widely used membrane model due to its well defined and controlled structure as well as versatility in composition [12][13][14][15][16][17][18][19]. The molecular interaction with dissolved drug component is monitored by the increase of surface pressure allowing to deduce its penetration ability [20][21][22][23].…”