A Comprehensive Model for Packing and Hydration for Amyloid Fibrils of β2-Microglobulin
A Comprehensive Model for Packing and Hydration for Amyloid Fibrils of β2-Microglobulin
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DOI：
10.1074/jbc.m806939200
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发表时间：
2009-01-23
影响因子：
4.8
通讯作者：
Goto, Yuji
中科院分区：
文献类型：
--
作者：
Lee, Young-Ho;Chatani, Eri;Goto, Yuji
体积可以提供大分子如蛋白质在溶液中的信息结构描述，因为最终的体积结果伴随着残留物之间以及蛋白质内外的残留物和沃茨之间的堆积效应的精确平衡。在这里，我们进行了系统的研究体积性质的β（2）-微球蛋白（β 2-m）和淀粉样蛋白的核心肽，K3，使用高精度密度计的淀粉样蛋白的构象。从酸变性β 2-m到成熟淀粉样蛋白原纤维的转变伴随着部分比容的正变化，其大于从酸变性β 2-m到天然结构的转变所观察到的变化。这些数据表明，成熟的淀粉样蛋白原纤维体积比天然结构，因为稀疏的侧链堆积密度。与此相反，从无规卷曲的K3的成熟淀粉样原纤维的形成，其次是相当大的减少，在部分特定的体积，这表明一个高度紧凑的核心结构。有趣的是，β（2）-m的未成熟淀粉样原纤维的体积介于β（2）- m和K3的成熟原纤维之间，这是因为它们的中心具有核心结构，而核心周围的区域相对不致密，具有大量水合作用。这些体积差异是由主链主导的原纤维形成的本质造成的。我们建议这三种类型的原纤维说明包装和水合状态的综合模型。
Volume can provide informative structural descriptions of macromolecules such as proteins in solution because a final volumetric outcome accompanies the exquisite equipoise of packing effects between residues, and residues and waters inside and outside proteins. Here we performed systematic investigations on the volumetric nature of the amyloidogenic conformations of beta(2)-microglobulin (beta 2-m) and its amyloidogenic core peptide, K3, using a high precision densitometer. The transition from the acid-denatured beta 2-m to the mature amyloid fibrils was accompanied by a positive change in the partial specific volume, which was larger than that observed for the transition from the acid-denatured beta(2)-m to the native structure. The data imply that the mature amyloid fibrils are more voluminous than the native structure because of a sparse packing density of side chains. In contrast, the formation of the mature amyloid-like fibrils of the K3 from the random coil was followed by a considerable decrease in the partial specific volume, suggesting a highly compact core structure. Interestingly, the immature amyloid-like fibrils of beta(2)-m exhibited a volume intermediate between those of the mature fibrils of beta(2)- m and K3, because of the core structure at their center and the relatively noncompact region around the core with much hydration. These volumetric differences would result from the nature of main-chain-dominated fibrillogenesis. We suggest comprehensive models for these three types of fibrils illustrating packing and hydrational states.