Macromolecular crowding accelerates amyloid formation by human apolipoprotein C-II
Macromolecular crowding accelerates amyloid formation by human apolipoprotein C-II
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DOI：
10.1074/jbc.m110429200
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发表时间：
2002-03-08
影响因子：
4.8
通讯作者：
Howlett, GJ
中科院分区：
文献类型：
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作者：
Hatters, DM;Minton, AP;Howlett, GJ
人载脂蛋白C-II（apoC-H）在生理pH和盐浓度下在无脂溶液中缓慢形成淀粉样纤维（Hatters，D. M.，麦克菲克角E、劳伦斯湖J.，索耶，W. H、和Howlett，G.（2000）Biochemistry 39，8276-8283）。溶液浊度、硫磺素T反应性和可沉淀聚集体的量的时间依赖性的测量揭示，通过添加浓度超过20 g/L的惰性聚合物葡聚糖T10，淀粉样蛋白形成的速率和程度显著增加。高葡聚糖浓度不改变蛋白质的二级结构、纤维形态或载脂蛋白C-H淀粉样蛋白的硫磺素T和刚果红结合能力。分析超离心研究表明，单体apoC-II不与葡聚糖显着相关。淀粉样蛋白形成的总速率对葡聚糖浓度的依赖性可以用一个简单的非特异性体积排阻模型来定量解释。该模型预测，在一个生理流体中的大分子的体积分数占用的增加可以非特异性地加速任何淀粉样蛋白的淀粉样纤维的形成。
Human apolipoprotein C-II (apoC-H) slowly forms amyloid fibers in lipid-firee solutions at physiological pH and salt concentrations (Hatters, D. M., MacPhec, C. E., Lawrence, L. J., Sawyer, W. H., and Howlett, G. J. (2000) Biochemistry 39, 8276-8283). Measurements of the time dependence of solution turbidity, thioflavin T reactivity, and the amount of sedimentable aggregate reveal that the rate and extent of amyloid formation are significantly increased by the addition of an inert polymer, dextran T10, at concentrations exceeding 20 g/liter. High dextran concentrations do not alter the secondary structure of the protein, fiber morphology, or the thioflavin T and Congo Red binding capacity of apoC-H amyloid. Analytical ultracentrifugation studies show that monomeric apoC-II does not associate significantly with dextran. The observed dependence of the overall rate of amyloid formation on dextran concentration may be accounted for quantitatively by a simple model for nonspecific volume exclusion. The model predicts that an increase in the fractional volume occupancy of macromolecules in a physiological fluid can nonspecifically accelerate the formation of amyloid fibers by any amyloidogenic protein.