N. Palaniyar et al., Domains of surfactant protein A that affect protein oligomerization, lipidstructure and surface tension, COMP BIOC A, 129(1), 2001, pp. 109-127
Citations number
112
Categorie Soggetti
Animal Sciences",Physiology
Journal title
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY
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.