Fibril formation from the amyloid-beta peptide is governed by a dynamic equilibrium involving association and dissociation of the monomer.
Fibril formation from the amyloid-beta peptide is governed by a dynamic equilibrium involving association and dissociation of the monomer.
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DOI：
10.1007/s12551-016-0217-7
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发表时间：
2017-02-01
影响因子：
--
通讯作者：
Hoshino, Masaru
中科院分区：
文献类型：
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作者：
Hoshino, Masaru
在这里，我回顾了水溶性单体淀粉样β (Abeta) 肽转化为组织良好的超分子复合物（称为淀粉样原纤维）的分子机制。根据实验结果从理论上考虑了淀粉样蛋白形成的机制，并强调了淀粉样蛋白原纤维与三维晶体的结构和机制的相似性。描述了文献中的许多重要结果。其中包括观察到单体缔合和解离速率常数的正确比例是形成组织良好的淀粉样蛋白原纤维的关键。讨论了β-淀粉样蛋白结构的动态性质，以及在掺入淀粉样蛋白原纤维之前短暂形成发夹样折叠的可能必然要求。在明显沉默的滞后期期间可能会出现多轮单体缔合和解离事件。在这些结合/解离事件中，Abeta 肽的 C 末端区域之间的相互作用似乎更受青睐。这种以“试错”方式发生的结合和解离事件可能是形成组织良好的淀粉样原纤维的重要要求。
Here I review the molecular mechanisms by which water-soluble monomeric amyloid-beta (Abeta) peptides are transformed into well-organized supramolecular complexes called amyloid fibrils. The mechanism of amyloid formation is considered theoretically on the basis of experimental results, and the structural and mechanistic similarities of amyloid fibrils to three-dimensional crystals are highlighted. A number of important results from the literature are described. These include the observation that a correct ratio of monomer association and dissociation rate constants is key for formation of well-organized amyloid fibrils. The dynamic nature of the amyloid-beta structure is discussed, along with the possibly obligate requirement of the transient formation of a hairpin-like fold prior to its incorporation into amyloid fibrils. Many rounds of monomer association and dissociation events may be present during an apparently silent lag-period. Amongst these association/dissociation events, interaction between the C-terminal regions of the Abeta peptide seems to be more favored. Such association and dissociation events occurring in a "trial-and-error" fashion may be an important requirement for the formation of well-organized amyloid fibrils.