Protofilaments, filaments, ribbons, and fibrils from peptidomimetic self-assembly: Implications for amyloid fibril formation and materials science
Protofilaments, filaments, ribbons, and fibrils from peptidomimetic self-assembly: Implications for amyloid fibril formation and materials science
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DOI：
10.1021/ja9937831
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发表时间：
2000-06-07
影响因子：
15
通讯作者：
Kelly, JW
中科院分区：
文献类型：
--
作者：
Lashuel, HA;LaBrenz, SR;Kelly, JW
破译β -片介导的自组装机制对于理解淀粉样蛋白纤维的形成和多肽材料的制备至关重要。在此，我们报道了一种简单的拟肽，它可以自我组装成多态的β片四级结构，包括原丝、细丝、原纤维和带状，这让人想起淀粉样蛋白肽a β、降钙素和胰淀素所显示的高度有序的结构。在某些情况下，可以通过控制pH值、缓冲液组成和离子强度来控制和指定四元结构的分布。控制β -薄片介导组装的能力利用了依赖于四级结构的pK(a)扰动。生物物理方法，包括分析超离心研究以及远紫外圆二色性和FT-IR光谱表明，相关的二级和四级结构变化介导了拟肽的自组装。电子和原子力显微镜显示，拟肽组装涉及许多四元结构中间体，这些中间体似乎以收敛的方式自组装，从而提供越来越复杂的四元结构。控制组装途径和最终提供的四级结构的能力应该被证明在破译淀粉样纤维形成和非共价大分子结构构建的四级结构要求方面特别有用。
Deciphering the mechanism(s) of beta-sheet mediated self-assembly is essential for understanding amyloid fibril formation and for the fabrication of polypeptide materials. Herein, we report a simple peptidomimetic that self-assembles into polymorphic beta-sheet quaternary structures including protofilaments, filaments, fibrils, and ribbons that are reminiscent of the highly ordered structures displayed by the amyloidogenic peptides A beta, calcitonin, and amylin. The distribution of quaternary structures can be controlled by and in some cases specified by manipulating the pH, buffer composition, and the ionic strength. The ability to control beta-sheet-mediated assembly takes advantage of quaternary structure dependent pK(a) perturbations. Biophysical methods including analytical ultracentrifugation studies as well as far-UV circular dichroism and FT-IR spectroscopy demonstrate that linked secondary and quaternary structural changes mediate peptidomimetic self-assembly. Electron and atomic force microscopy reveal that peptidomimetic assembly involves numerous quaternary structural intermediates that appear to self-assemble in a convergent fashion affording quaternary structures of increasing complexity. The ability to control the assembly pathway(s) and the final quaternary structure(s) afforded should prove to be particularly useful in deciphering the quaternary structural requirements for amyloid fibril formation and for the construction of noncovalent macromolecular structures.