2014 Fiscal Year Annual Research Report
過飽和の解消による蛋白質の異常凝集体の形成に関する研究
| Project/Area Number |
14J04433
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| Research Institution | Osaka University |
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Principal Investigator |
林 雨曦 大阪大学, 理学研究科, 特別研究員(DC1)
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| Project Period (FY) |
2014-04-25 – 2017-03-31
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| Keywords | protein aggregation / supersaturation / solubility / phase diagram |
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| Outline of Annual Research Achievements |
Aberrant Protein aggregation is essential for more than 30 serious diseases, such as Alzheimer's disease and type Ⅱ diabetes. A better understanding of the mechanism leading to protein aggregation is very important for the treatment and prevention of these diseases. In my previous study, I constructed phase diagrams of lysozyme to explain the role of solubility and supersaturation in alcohol-induced lysozyme aggregation. Cytochrome c aggregation was investigated in the same system this year for deepening the understanding of protein aggregation.
Apocytochrome c and Ag-apocytchrome c were prepared from holocytochrome c using silver sulfate method. Then, the aggregation behavior of three types of cytochrome c were examined in water/alcohol mixtures. Based on the results, phase diagrams of three types of cytochrome c were contrasted. By comparing the phase diagrams, we found that cytochrome c might be inherently low amyloidogenic, and removing heme group decreased cytochrome c solubility, widening the amoprphous region. My results further suggested that protein aggregation was not correlated with protein secondary structure content.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The aggregation behavior of three types of cytochrome c was examined as the plan, and phase diagrams of them were successfully constructed at the same time. Paper of this study is in preparation now.
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| Strategy for Future Research Activity |
I examined the aggregation behavior of two model globular proteins, lysozyme and cyotchrome c, in water/alcohol mixtures, and constructed their phase diagrams depending on the results. I will study the aggregation of intrinsically disordered proteins in the next. Amyloid β(1-40) and α-synuclein will be employed because of their close association with Alzheimer's disease and Parkinson's disease.
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