Physicochemical mechanisms of aggregation and fibril formation of α-synuclein and apolipoprotein A-I
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- Ohgita Takashi
- Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University Center for Instrumental Analysis, Kyoto Pharmaceutical University
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- Kono Hiroki
- Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University
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- Namba Norihiro
- Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University
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- Saito Hiroyuki
- Laboratory of Biophysical Chemistry, Kyoto Pharmaceutical University
抄録
<p>Deposition and accumulation of amyloid fibrils is a hallmark of a group of diseases called amyloidosis and neurodegenerative disorders. Although polypeptides potentially have a fibril-forming propensity, native proteins have evolved into proper functional conformations to avoid aggregation and fibril formation. Understanding the mechanism for regulation of fibril formation of native proteins provides clues for the rational design of molecules for inhibiting fibril formation. Although fibril formation is a complex multistep reaction, experimentally obtained fibril formation curves can be fitted with the Finke-Watzky (F-W) two-step model for homogeneous nucleation followed by autocatalytic fibril growth. The resultant F-W rate constants for nucleation and fibril formation provide information on the chemical kinetics of fibril formation.</p><p>Using the F-W two-step model analysis, we investigated the physicochemical mechanisms of fibril formation of a Parkinson’s disease protein α-synuclein (αS) and a systemic amyloidosis protein apolipoprotein A-I (apoA-I). The results indicate that the C-terminal region of αS enthalpically and entropically suppresses nucleation through the intramolecular interaction with the N-terminal region and the intermolecular interaction with existing fibrils. In contrast, the nucleation of the N-terminal fragment of apoA-I is entropically driven likely due to dehydration of large hydrophobic segments in the molecule. Based on our recent findings, we discuss the similarity and difference of the fibril formation mechanisms of αS and the N-terminal fragment of apoA-I from the physicochemical viewpoints.</p>
収録刊行物
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- Biophysics and Physicobiology
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Biophysics and Physicobiology 21 (1), n/a-, 2024
一般社団法人 日本生物物理学会
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詳細情報 詳細情報について
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- CRID
- 1390861847633745536
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- ISSN
- 21894779
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
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- 抄録ライセンスフラグ
- 使用不可