Sarker, Muzaddid (2006) NMR structural studies of lung surfactant protein B (SP-B) peptides. Masters thesis, Memorial University of Newfoundland.
- Accepted Version
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Mammalian lungs are composed of millions of tiny air sacs called alveoli where gas exchange takes place. The inner surface of alveoli is coated by an aqueous layer to prevent it from drying up. However, because the attraction between water molecules is stronger than the force between water and air, a surface tension is created at the air-water interface. The tension tends to collapse the alveoli and increase the work of breathing. Lung surfactant is a material that counteracts these tendencies by reducing the surface tension to extremely low values and thus prevents the alveolar collapse and also eases the work of breathing. The lung surfactant material is a mixture of lipids and proteins. Surfactant Protein B (SP-B) is an essential component of the surfactant and is thought to function by facilitating large-scale rearrangement of the lipid molecules and stabilizing the structures. However, neither the structural basis for this ability nor the physiological ramifications of lipid rearrangements are yet understood. SP-B is a lipid-associated hydrophobic protein, which makes it difficult to address with X-ray or conventional solution NMR structural techniques. These difficulties have been addressed in NMR structural studies by the use of fluorinated organic solvents and lipid micelles to solubilize the proteins. The present work has focused on SP-BcTERM and Mini-B, two peptide fragments of SP-B that retain significant biological activity of the full-length protein. The structural features of these peptides were studied using high-resolution solution NMR. Firstly, the conformational features of SP-BcTERM and its interactions with lipids were investigated in micelles mimicking the lipid environment in the lungs. The peptide exhibited the ability to cause aggregation of micelles formed from lipids similar to those found in lungs. This was indicative of the large-scale lipid rearrangement and stabilization of structures facilitated by SP-B in natural surfactant. In the second and main phase of current research, the structure of Mini-B was determined in the structureinducing fluorinated organic solvent hexafluoroisopropanol (HFIP). The peptide was found to consist of two a-helices at the termini connected by an unstructured loop at the middle. These studies help to define the structural properties that underlie SP-B's function and provide a platform to probe the lipid-protein interactions that are responsible for the ability of lung surfactant to dramatically lower the surface tension at the air-water interface in alveoli.
|Item Type:||Thesis (Masters)|
|Additional Information:||Includes bibliographical references (pages 103-112).|
|Department(s):||Science, Faculty of > Physics and Physical Oceanography|
|Library of Congress Subject Heading:||Lipoproteins; Pulmonary surfactant|
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