Kinetic control in the folding of two proteins /
The folding pathways of the proteins human transthyretin and bacterial luciferase from Vibrio harveyi are under kinetic control. Detailed studies were carried out using mutants of these two proteins to examine their folding pathways relative to the wild type proteins in order to gain insight into t...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2001.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=728908651&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | The folding pathways of the proteins human transthyretin and bacterial luciferase from Vibrio harveyi are under kinetic control. Detailed studies were carried out using mutants of these two proteins to examine their folding pathways relative to the wild type proteins in order to gain insight into the mechanisms of folding. The conversion of tetrameric transthyretin into amyloid fibrils is implicated in several types of amyloid disease. Mutant forms of the protein appear to favor this conversion via a monomeric, rearranged intermediate form of the protein, resulting in a more aggressive disease state. Kinetic denaturation data for wild type and the amyloidogenic mutant V30M reveal two-phase sequential unfolding mechanisms for both forms of transthyretin. The much more highly amyloidogenic mutant L55P exhibits only a single phase in its denaturation, implying a simpler mechanism of unfolding. The data indicate that the L55P variant denatures by a different mechanism than wild type and the V30M variant, which may imply easier access to the amyloidogenic intermediate which forms the amyloid fibrils, leading to the observed greater amyloidogenicity of this variant. The equilibrium unfolding curves were examined for four mutants of bacterial luciferase which were designed to cause changes near the subunit interface of this dimeric protein. The protein exists in its native state as a heterodimer of homologous alpha and beta subunits, but can also form a kinetically trapped homodimer of beta subunits. The heterodimer and homodimer are known to have very different thermodynamic and kinetic profiles, but the source of these differences is not known. The data collected for the four luciferase mutants reveal that the structural features of the subunit interface do not seem to make a significant contribution to the observed differences between the two dimers. |
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| Item Description: | Vita. "Major Subject: Chemistry". |
| Physical Description: | xii, 171 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 134-140). |