Amyloid formation: an emulation of matrix protein assembly?
Amyloid formation: an emulation of matrix protein assembly?
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DOI：
10.1080/13506120400016265
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发表时间：
2004-12-01
影响因子：
5.5
通讯作者：
Stevens, FJ
中科院分区：
文献类型：
--
作者：
Stevens, FJ
虽然现在有20多种不同的蛋白质与淀粉样变性有关，但这些纤维具有许多共同的特性。尽管亚基蛋白质的一级和三级结构不同，但组装后的纤维显示出相似的形态、刚果红的结合、与硫代黄素T的相互作用、与血清淀粉样蛋白P组分、载脂蛋白E、几种糖胺多聚糖、晚期糖基化终末产物的受体形成的复合体，以及与一些单抗的交叉识别。因此，淀粉样蛋白的产生机制很可能涉及一个普通的过程，在降解天然构象的条件下，大多数蛋白质(如果不是全部的话)都能引起这种过程。另一些人提出，β-螺旋或β-卷曲构象可能是纤维构象的统一元素。一些已经进化成生理上有用的淀粉样纤维的蛋白质，以及与病理性淀粉样变性相关的声波蛋白质，表现出可能促进β-卷曲或β-螺旋形成的序列重复模式。对两种天然淀粉样蛋白Curli和人PMEL 17的穿线分析表明，它们的一级结构与β三明治和β螺旋构象都是相容的，这表明可能存在天生的构象柔韧性。此外，这些结果可能表明，与构象疾病相关的一些蛋白质的错误折叠形式可能是与疾病通过进化联系在一起的其他蛋白质的天然构象。最后，由于许多基质和结构蛋白都含有大量的串联重复序列元件，我们认为纤维形成的机制从根本上与细胞和组织生成所必需的一般蛋白质组装过程有关。
Although more than 20 different proteins are now associated with the amyloidoses, the fibrils share many properties. Despite disparity in primary and tertiary structures of the subunit proteins, assembled,fibrils exhibit similar morphology, binding of Congo red, interaction with Thioflavine T, formation of complexes with serum amyloid P component, apolipoprotein E, several glycosaminoglycans, the receptor for advanced glycation endproducts and cross-recognition by some monoclonal antibodies. Thus, it is probable that the mechanism of amyloid generation involves a generic process that can be evoked by most, if not all, proteins under conditions that degrade the native conformation. As suggested by others, the beta-helix or beta-roll conformation may be the unifying element of fibril conformations. Several proteins that have evolved to form physiologically useful amyloid like fibrils, as well as sonic proteins associated with pathological amyloidoses, exhibit sequence repeat patterns that may facilitate beta-roll or beta-helix formation. Threading analyses of 2 natural amyloid-forming proteins, curli and human Pmel 17, indicate compatibility of their primary structures with both beta sandwich and beta-helix conformations, suggesting a possible innate conformational pliability. In addition, these results may suggest that the misfolded form of some proteins that are associated with conformational disease may be the native conformation of other proteins to which the-ill are linked by evolution. Finally, since many matrix and structural proteins are known to incorporate numerous tandem repeat sequence elements, we propose that the mechanism of fibril formation is fundamentally related to a general protein assembly process that is integral to the generation of cells and tissues.