Several functions have been attributed to the oligosaccharide moiety of N-asparaginyl-linked glycoproteins including intracellular sorting and trafficking of macromolecules, serving as recognition sites for the binding of substances at the cell surface, and mediating cell-cell interactions. Structural information concerning the oligosaccharide is necessary to understand the role of the oligosaccharide moiety in these phenomena. The pulmonary surfactant, which is composed of lipids and proteins, lines the air spaces of the lungs and prevents alveolar collapse during expiration by reducing the surface tension at the air/liquid interface. One of the surfactant associated proteins is a glycoprotein of molecular weight 26-35 Kdaltons, referred to as SP26-35. SP26-35 not only aids in the ability of the surfactant to reduce surface tension but also has been implicated in the process of uptake and/or degradation of the surfactant. By analogy to other systems, the oligosaccharide moiety may play an important role in this process. Thus studies to address the structural features of the oligosaccharide(s) of SP26-35 isolated from rat surfactant are proposed. The number of oligosaccharide chains per protein molecule will be determined by comparing the amount of oligosaccharide released by peptide:N-glycosidase to the number of N-terminal amino acids in the same amount of protein. The extent of glycosylation occurring at each of the two possible glycosylation sites will also be determined. Finally, the major structural features of the oligosaccharides (from each individual site) will be studied using serial lectin chromatography and high pressure liquid chromatography. These studies will allow the development of additional experiments to study the role the oligosaccharide may have in the synthesis, uptake, or recycling of the pulmonary surfactant. This type of basic information concerning the structure, function and interrelationships of the components of the pulmonary surfactant must be available before an effective means of treating surfactant deficiencies, such as neonatal respiratory distress syndrome, and abnormalities can be developed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15HL040440-01
Application #
3440025
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1988-05-01
Project End
1989-06-01
Budget Start
1988-05-01
Budget End
1989-06-01
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
St. Mary's College
Department
Type
Schools of Arts and Sciences
DUNS #
City
Notre Dame
State
IN
Country
United States
Zip Code
46556