Domains of surfactant protein A that affect protein oligomerization, lipidstructure and surface tension

Surfactant protein A (SP-A) is an abundant protein found in pulmonary surfa ctant which has been reported to have multiple functions. In this review, w e focus on the structural importance of each domain of SP-A in the function s of protein oligomerization, the structural organization of lipids and the surface-active properties of surfactant, with an emphasis on ultrastructur al analyses. The N-terminal domain of SP-A is required for disulfide-depend ent protein oligomerization, and for binding and aggregation of phospholipi ds, but there is no evidence that this domain directly interacts with lipid membranes. The collagen-like domain is important for the stability and oli gomerization of SP-A. It also contributes shape and dimension to the molecu le, and appears to determine membrane spacing in lipid aggregates such as c ommon myelin and tubular myelin. The neck domain of SP-A is primarily invol ved in protein trimerization, which is critical for many protein functions, but it does not appear to be directly involved in lipid interactions. The globular C-terminal domain of SP-A clearly plays a central role in lipid bi nding, and in more complex functions such as the formation and/or stabiliza tion of curved membranes. In recent work, we have determined that the maint enance of low surface tension of surfactant in the presence of serum protei n inhibitors requires cooperative interactions between the C-terminal and N -terminal domains of the molecule. This effect of SP-A requires a high degr ee of oligomeric assembly of the protein, and may be mediated by the activi ty of the protein to alter the form or physical state of surfactant lipid a ggregates. (C) 2001 Elsevier Science Inc. All rights reserved.