Intrinsic structural differences in the N-terminal segment of pulmonary surfactant protein SP-C from different species

Predictive studies suggest that the known sequences of the N-terminal segme nt of surfactant protein SP-C from animal species have an intrinsic tendenc y to form p-turns, but there are important differences on the probable loca tion of these motifs in different SP-C species. Our hypothesis is that intr insic structural determinants of the sequence of the N-terminal region of S P-C could define conformation, acylation and perhaps surface properties of the mature protein. To test this hypothesis we have synthesized peptides co rresponding to the 13-residue N-terminal sequence of porcine and canine SP- C, and studied their structural behaviour in solution and in phospholipid b ilayers and monolayers. In these peptides, leucine at position 1 of both se quences has been replaced by tryptophan in order to allow their study by fl uorescence spectroscopy. Far-u.v, circular dichroism spectra of the peptide s in aqueous and organic solutions and in phospholipid micelles or vesicles are consistent with predicted conformational differences between the porci ne and the canine sequences. Both families of peptides showed changes in th eir fluorescence emission spectra in the presence of phospholipids that wer e consistent with spontaneous lipid/peptide interactions. Both canine and p orcine peptides were able to form monolayers at air-liquid interfaces, the canine peptides occupying lower area/molecule and being compressible to hig her pressures than the porcine sequences. The peptides also shifted the iso therms and perturbed the: packing of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) monolayers, the effects being al ways higher in anionic than in zwitterionic lipids, and also substantially higher in films containing canine peptide in comparison to porcine peptide. Acylation of cysteines at the N-terminal end of SP-C may modulate these in trinsic conformational features and the changes induced could be important for the development of its surface activity. (C) 2001 Elsevier Science Inc. All rights reserved.