Flow-induced alignment of amyloid protofilaments revealed by linear dichroism
Flow-induced alignment of amyloid protofilaments revealed by linear dichroism
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DOI：
10.1074/jbc.m611738200
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发表时间：
2007-03-23
影响因子：
4.8
通讯作者：
Goto, Yuji
中科院分区：
文献类型：
--
作者：
Adachi, Rumi;Yamaguchi, Kei-ichi;Goto, Yuji
各种严重淀粉样变性（包括阿尔茨海默病和朊病毒病）的基础上的u淀粉样原纤维形成特征性沉积物，其中具有不分支和刚性形态的线性原纤维横向或径向缔合，例如淀粉样蛋白β的径向老年淀粉样斑块。为了阐明这些高级淀粉样蛋白沉积物的形成，研究流变学是重要的。β 2-微球蛋白（一种导致透析相关淀粉样变性的蛋白质）的22个残基K3肽片段在20%（v/v）2，2，2-三氟乙醇和10 mM HCl（pH值类似于2）中形成长而均匀的原纤维样原纤维。在这里，使用圆二色性和线性二色性，我们观察到流动诱导的原纤维排列。远紫外和近紫外线性二色光谱分析表明，主链羰基的π-π跃迁矩和Tyr（26）侧链的L-b跃迁矩均平行于原纤维轴取向，揭示了淀粉样蛋白原丝的结构细节。此外，流动诱导的圆二色性或线性二色性信号的强度严重依赖于纤维的长度和类型，这表明它们可用于检测和表征淀粉样蛋白纤维。
uAmyloid fibrils underlying various serious amyloidoses including Alzheimer and prion diseases form characteristic deposits in which linear fibrils with an unbranched and rigid morphology associate laterally or radially, e.g. radial senile amyloid plaques of amyloid beta. To clarify the formation of these high order amyloid deposits, studying the rheology is important. A 22-residue K3 peptide fragment of beta(2)-microglobulin, a protein responsible for dialysis-related amyloidosis, forms long and homogeneous protofilament-like fibrils in 20% (v/v) 2,2,2-trifluoroethanol and 10 mM HCI (pH similar to 2). Here, using circular dichroism and linear dichroism, we observed the flow-induced alignment of fibrils. Analysis of far- and near-UV linear dichroism spectra suggested that both the net pi-pi transition moment of the backbone carbonyl group and L-b transition moment of the Tyr(26) side chain are oriented in parallel to the fibril axis, revealing the structural details of amyloid protofilaments. Moreover, the intensities of flow-induced circular dichroism or linear dichroism signals depended critically on the length and type of fibrils, suggesting that they are useful for detecting and characterizing amyloid fibrils.