Disulfide bonds prevent aggregation of globular proteins by stabilizing the native state. However, a disulfide bond within a disordered state may accelerate amyloidogenic nucleation by navigating fluctuating polypeptide chains towards an orderly assembly of β-sheets. Here, the self-assembly behavior of Glu-Cys-(Glu)₄-Cys-Glu peptide (E₆C₂), in which an intrachain disulfide bond is engineered into an amyloidogenic homopolypeptide motif, is investigated. To this end, the Thioflavin T (ThT) fluorescence kinetic assay is combined with infrared spectroscopy, circular dichroism (CD), atomic force microscopy (AFM) and Raman scattering measurements. Regardless of whether the disulfide bond is intact or reduced, E₆C₂ monomers remain disordered within a broad range of pH. On the other hand, only reduced E₆C₂ self-assembles into amyloid fibrils with the unique infrared traits indicative of three-center hydrogen bonds involving main-chain carbonyl as a bifurcating acceptor and main-chain NH and side-chain –COOH groups as hydrogen donors: the bonding pattern observed in so-called β₂-fibrils. AFM analysis of β₂-E₆C₂ reveals tightly packed rectangular superstructures whose presence coincides with strong chiroptical properties. Our findings suggest that formation of chiral amyloid superstructures may be a generic process accessible to various substrates, and that the fully extended conformation of a poly-Glu chain is a condition sine qua non for self-assembly of β₂-fibrils.

二硫键通过稳定天然状态防止球状蛋白聚集。但是，处于无序状态的二硫键可能会通过使波动的多肽链朝β-sheets的有序组装方向移动，从而加快淀粉样蛋白成核作用。在此，研究了其中将链内二硫键工程化为淀粉样生成性均多肽基序的Glu-Cys-（Glu）₄ -Cys-Glu肽（E ₆ C ₂）的自组装行为。为此，硫黄素T（ThT）荧光动力学分析与红外光谱，圆二色性（CD），原子力显微镜（AFM）和拉曼散射测量相结合。不管二硫键是完整的还是还原的，E ₆ C ₂单体在很宽的pH范围内仍然无序。另一方面，只有还原的E ₆ C ₂自组装为淀粉样原纤维，具有独特的红外特性，表明三中心氢键涉及主链羰基作为分叉受体，主链NH和侧链–COOH基团作为氢供体：所述粘合图案中观察到的所谓的β _2个-fibrils。的βAFM分析₂ -E ₆ Ç ₂揭示了紧密堆积的矩形上部结构，其存在与强烈的按摩特性相吻合。我们的发现表明手性淀粉样上层建筑其形成可能对各种基材访问的通用过程，并且聚谷氨酸链的完全伸展构象为自组装β的必要条件_2个-fibrils。