Formation of Two Different Types of Oligomers in the Early Phase of pH-Induced Aggregation of the Alzheimer Aβ(12-28) Peptide
Formation of Two Different Types of Oligomers in the Early Phase of pH-Induced Aggregation of the Alzheimer Aβ(12-28) Peptide
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DOI：
10.1021/jp305015g
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发表时间：
2012-10-18
影响因子：
3.3
通讯作者：
Barth, Andreas
中科院分区：
文献类型：
--
作者：
Mandal, Paulami;Eremina, Nadejda;Barth, Andreas
用时间分辨红外光谱和圆二色光谱研究了具有保护和未保护末端的阿尔茨海默氏肽A β（12-28）聚集过程的早期阶段。在时间分辨实验中的聚集是由1-（2-硝基苯基）乙基硫酸盐（笼状硫酸盐）的光解引起的pH值快速下降引发的。红外光谱表明来自两种形式的A β（12-28）肽的两种不同类型的聚集体。一种类型具有小的和/或扭曲的β片层，在1627 cm（-1）处具有β片层带，它们形成快（在60 ms内），可能来自初始聚集体，并且它们的光谱特征与β桶结构一致。另一种类型在秒至分钟的时间尺度上相对缓慢地从非结构化单体产生，并且在比第一种类型更低的pH下形成。这些β片层是反平行的、平面的、大的，并且显示出在1622 cm（-1）处的吸收带，该吸收带在12 min内移位到1617 cm（-1），其中大部分移位发生在10 s内。
The early phase in the aggregation process of the Alzheimer's peptide A beta(12-28) with both protected and unprotected ends was studied by time-resolved infrared spectroscopy and circular dichroism spectroscopy. Aggregation in the time-resolved experiments was initiated by a rapid pH drop caused by the photolysis of 1-(2-nitrophenyl)ethyl sulfate (caged sulfate). The infrared spectra indicate two different types of aggregates from both versions of the A beta(12-28) peptide. One type has small and/or twisted beta sheets with a beta-sheet band at 1627 cm(-1), They form fast (within 60 ms), presumably from initial aggregates, and their spectral signature is consistent with a beta-barrel structure. The other type arises relatively slowly from unstructured monomers on the seconds-to-minutes time scale and forms at lower pH than the first type. These beta sheets are antiparallel, planar, and large and show an absorption band at 1622 cm(-1) that shifts to 1617 cm(-1) in 12 min with most of the shift occurring in 10 s.