Structural changes of surfactant protein A induced by cations reorient the protein on lipid bilayers.
Surfactant protein A (SP-A) is an octadecameric hydrophilic glycoprotein and is the major protein component of pulmonary surfactant. This protein complex plays several roles in the body, such as regulation of surfactant secretion, recycling and adsorption of surfactant lipids, and non-serum-induced immune response. Many of SP-A's activities are dependent upon the presence of cations, especially calcium. Here, we have studied in vitro the effect of cations on the interaction of purified bovine SP-A with phospholipid vesicles made of dipalmitoylphosphatidylcholine and unsaturated phosphatidylcholine. We have found that SP-A octadecamers exist in an "opened-bouquet" conformation in the absence of cations and interact with lipid membranes via one or two globular headgroups. Calcium-induced structural changes in SP-A lead to the formation of a clearly identifiable stem in a "closed-bouquet" conformation. This change, in turn, seemingly results in all of SP-A's globular headgroups interacting with the lipid membrane surface and with the stem pointing away from the membrane surface. These results represent direct evidence that the headgroups of SP-A (comprising carbohydrate recognition domains), and not the stem (comprising the amino-terminus and collagen-like region), interact with lipid bilayers. Our data support models of tubular myelin in which the headgroups, not the tails, interact with the lipid walls of the lattice.
Department of Molecular Biology & Genetics, The University of Guelph, Guelph, Ontario, N1G 2W1, Canada.
N
N
Palaniyar
R A
RA
Ridsdale
C E
CE
Holterman
K
K
Inchley
F
F
Possmayer
G
G
Harauz
D000818:Animals; D001665:Binding Sites; D002118:Calcium; D002412:Cations; D002417:Cattle; D006023:Glycoproteins / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000737:chemistry; D008854:Microscopy, Electron; D011487:Protein Conformation; D011510:Proteolipids / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure
D002412:Cations; D006023:Glycoproteins; D008051:Lipid Bilayers; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D002118:Calcium