Lung Surfactant Protein A (SP-A) Interactions with Model Lung Surfactant Lipids and an SP-B Fragment

摘要

Surfactant protein A (SP-A) is the most abundantnprotein component of lung surfactant, a complex mixture ofnproteins and lipids. SP-A performs host defense activities andnmodulates the biophysical properties of surfactant in concertednaction with surfactant protein B (SP-B). Current models of lungnsurfactant mechanism generally assume SP-A functions in itsnoctadecameric form. However, one of the findings of this studynis that when SP-A is bound to detergent and lipid micelles thatnmimic lung surfactant phospholipids, it exists predominantly asnsmaller oligomers, in sharp contrast to the much larger formsnobserved when alone in water. These investigations were carried out in sodium dodecyl sulfate (SDS), dodecylphosphocholinen(DPC), lysomyristoylphosphatidylcholine (LMPC), lysomyristoylphosphatidylglycerol (LMPG), and mixed LMPC þ LMPGnmicelles, using solution and diffusion nuclear magnetic resonance (NMR) spectroscopy. We have also probed SP-A’s interactionnwith Mini-B, a biologically active synthetic fragment of SP-B, in the presence of micelles. Despite variations in Mini-B’sownninteractions with micelles of different compositions, SP-A is found to interact with Mini-B in all micelle systems and perhaps tonundergo a further structural rearrangement upon interacting with Mini-B. The degree of SP-Au0001Mini-B interaction appears to bendependent on the type of lipid headgroup and is likely mediated through the micelles, rather than direct binding.