| 研究実績の概要 |
This year I successfully finished the research project of cytochrome c (cyt c) aggregation (Lin et al. (2016) Langmuir 32, 2010-2022). I examined the aggregation behavior of the physiologically relevant two types of cyt c, metal-bound cyt c, and its fragment with high amyloidogenicity in alcohol/water mixtures. The aggregation propensity of holo cyt c was low due to high solubility, and markedly unfolded apo cyt c, lacking the heme prosthetic group, strongly promoted the propensity for amorphous aggregation with increases in hydrophobicity. Silver-bound apo cyt c increased the capacity of fibrillar aggregation due to subtle structural changes of apo cyt c by strong binding of silver. However, mature amyloid fibrils were not detected for any of the cyt c variants or its fragment, even with extensive ultrasonication. These results revealed the intrinsically low amyloidogenicity of cyt c, which is beneficial for its homeostasis and function by facilitating the folding and minimizing irreversible amyloid formation. I proposed that intrinsically low amyloidogenicity of cyt c is attributed to the low metastability of supersaturation. I also demonstrated that the phase diagram constructed based on solubility and aggregate type is useful for a comprehensive understanding of protein aggregation. Furthermore, amorphous aggregation, which is also viewed as a generic property of proteins, and amyloid fibrillation can be distinguished from each other by the metastability of supersaturation.
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