| Summary: | 碩士 === 國立臺灣大學 === 化學工程學研究所 === 97 === More than twenty different human proteins can fold abnormally into amyloid fibril deposits which may lead to lethal diseases. Despite extensive investigations on amyloid fibril formation, the detail of molecular mechanism remained rather elusive.
The current study is aimed at exploring the effect of thermal induced aggrefation of BSA samples at various pH values. Via numerous spectroscopic techniques and transmission electron microscopy, our results showed that bovine serum albumin samples at neutral condition (pH 7.4) and alkaline conditions (pH 9.0, and pH 10.0) can form amyloid fibril at 70oC. However, no obvious aggregation occurred at acidic condition (pH 2.0).
In the phase diagram analysis, we find several transition points through the heating processes except for BSA samples at pH 2.0. Our results demonstrate that BSA samples will form intermediates during the fibrillation processes.
Moreover, we use several ligands to further probe the structural changes of different domains. It could be concluded from our results that the breakage of the inter-domain between domain I and domain II prohibit the diamerization of BSA molecules and consequently inhibit the aggregation process.
According to the results from this study and the literature, we suggest that the fibrillation processes are facilitated by disulfide/thiol exchanges at 70oC at neutral and alkaline conditions. In addition, the breakage of inter-domain at acidic condition may suppress the fibrillation of BSA samples.
The outcome from this work may aid in comprehending the molecular mechanisms of fibrillogenesis of BSA at various pH conditions.
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