Templating Molecular Arrays in Amyloid's Cross-β Grooves
Templating Molecular Arrays in Amyloid's Cross-β Grooves
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DOI：
10.1021/ja902332s
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发表时间：
2009-07-29
影响因子：
15
通讯作者：
Lynn, David G.
中科院分区：
文献类型：
--
作者：
Childers, W. Seth;Mehta, Anil K.;Lynn, David G.
淀粉样蛋白纤维独立于初级氨基酸序列，具有共同的交叉P结构，并与组织化学染料刚果红(CR)结合。尽管CR在淀粉样蛋白诊断中得到了广泛的应用，但人们对其特异和特征的结合作用知之甚少。纤维的不溶性、形态的不均一性和多个可能的配基结合部位都限制了表征。在这里，我们利用了交叉贝塔纳米管的结构，它限制了潜在结合部位的数量，直接询问了交叉贝塔层压槽。结合到交叉β纳米管上的CR显示出苹果绿的干涉颜色，一个宽广的红移低能跃迁，K-d为1.9+/-0.5微米。定向电子衍射和线性二色性定义CR的取向平行于淀粉样长轴，并与层状凹槽共线。结合淀粉样蛋白的CR的广泛红移UV特征可以用半经验量子计算来解释，该计算支持J-和H-CR聚集体的精确网络的存在，阐明了淀粉样蛋白将分子组织成扩展阵列的能力，这是CR显著的诊断潜力的基础。
Amyloid fibers, independent of primary amino acid sequence, share a common cross-P structure and bind the histochemical dye Congo Red (CR). Despite extensive use of CR in amyloid diagnostics, remarkably little is known about the specific and characteristic binding interactions. Fibril insolubility, morphological inhomogeneity, and multiple possible ligand binding sites all conspire to limit characterization. Here, we have exploited the structure of cross-beta nanotubes, which limit the number of potential binding sites, to directly interrogate cross-beta laminate grooves. CR bound to cross-beta nanotubes displays the hallmark apple-green interference color, a broad red-shifted low energy transition, and a K-d of 1.9 +/- 0.5 mu M. Oriented electron diffraction and linear dichroism defines the orientation of CR as parallel to the amyloid long axis and colinear with laminate grooves. The broad red-shifted UV signature of CR bound to amyloid can be explained by semiempirical quantum calculations that support the existence of a precise network of J- and H-CR aggregates, illuminating the ability of the amyloid to organize molecules into extended arrays that underlie the remarkable diagnostic potential of CR.