Probing the relationship between the acid-induced denaturation of Transthyretin and amyloidosis /
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| Other Authors: | , , |
| Format: | Thesis Book |
| Language: | English |
| Published: |
1993.
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| Subjects: | |
| Online Access: | Link to ProQuest copy Link to OAKTrust copy |
| Abstract: | The pH-induced denaturation of Transthyretin (TTR) was studied in order to understand the biochemical basis of TTR's amyloidogenicity. The structural changes were monitored by UV, circular dichroism, and fluorescence spectroscopy. In addition, quaternary structural changes were specifically probed by an SDS PAGE-Detergent method developed in our laboratory. Amyloid fibrils from wild type TTR were created in vitro by incubating the protein at pH 4.5-3.6. Our experimental evidence suggest that an amyloidogenic denaturation intermediate is the precursor of TTR amyloid fibril formation. Denaturation and reconstitution experiments were performed with the amyloidogenic V30M TTR variant found in Familial Amyloidotic Polyneuropathy (FAP). Our data demonstrate that V30M TTR is denatured and able to form amyloid fibrils at a higher pH than wild type TTR. Reconstitution experiments have shown that the V30M TTR variants reassemble into the native tetrameric form at a significantly slower rate than the wild type protein. We conclude from these results that the increase in amyloidogenicity of FAP variants is due to a decreased in stability of the tetrameric TTR and / or the stabilization of an amyloidogenic folding intermediate. |
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| Item Description: | "Major subject: Chemistry." Vita. |
| Physical Description: | xii, 123 leaves : illustrations ; 28 cm |
| Bibliography: | Includes bibliographical references. |