Sunde M, Serpell L C, Bartlam M, Fraser P E, Pepys M B, Blake C C
University of Oxford, Rex Richards Building, South Parks Road, Oxford, OX1 3QU, UK.
J Mol Biol. 1997 Oct 31;273(3):729-39. doi: 10.1006/jmbi.1997.1348.
Tissue deposition of normally soluble proteins as insoluble amyloid fibrils is associated with serious diseases including the systemic amyloidoses, maturity onset diabetes, Alzheimer's disease and transmissible spongiform encephalopathy. Although the precursor proteins in different diseases do not share sequence homology or related native structure, the morphology and properties of all amyloid fibrils are remarkably similar. Using intense synchrotron sources we observed that six different ex vivo amyloid fibrils and two synthetic fibril preparations all gave similar high-resolution X-ray fibre diffraction patterns, consistent with a helical array of beta-sheets parallel to the fibre long axis, with the strands perpendicular to this axis. This confirms that amyloid fibrils comprise a structural superfamily and share a common protofilament substructure, irrespective of the nature of their precursor proteins.
正常情况下可溶的蛋白质以不溶性淀粉样纤维的形式在组织中沉积,与包括系统性淀粉样变性、成年型糖尿病、阿尔茨海默病和传染性海绵状脑病在内的严重疾病相关。尽管不同疾病中的前体蛋白不具有序列同源性或相关的天然结构,但所有淀粉样纤维的形态和特性都非常相似。利用高强度同步辐射源,我们观察到六种不同的离体淀粉样纤维和两种合成纤维制剂都给出了相似的高分辨率X射线纤维衍射图谱,这与平行于纤维长轴的β-折叠螺旋阵列一致,链垂直于该轴。这证实了淀粉样纤维构成一个结构超家族,并且共享一个共同的原纤维亚结构,而不论其前体蛋白的性质如何。