Ultrastructural organization of amyloid fibrils by atomic force microscopy
Ultrastructural organization of amyloid fibrils by atomic force microscopy
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DOI：
10.1016/s0006-3495(00)76560-x
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发表时间：
2000-12-01
影响因子：
3.4
通讯作者：
Davis, JJ
中科院分区：
文献类型：
--
作者：
Chamberlain, AK;MacPhee, CE;Davis, JJ
原子力显微镜已被用来研究淀粉样纤维的结构组织在体外产生的三个非常不同的多肽序列。所研究的系统是来自甲状腺素运载蛋白序列的10个残基的肽，牛磷脂酰肌醇-3 '-激酶的90个残基的SH 3结构域，和人野生型溶菌酶，一种含有四个二硫键的130个残基的蛋白质。结果表明，尽管所涉及的多肽种类的对比性质，但由不同类别的原纤维形成的结构之间存在明显的相似性。SH 3和溶菌酶原纤维通常由四个原丝组成，沿原纤维轴沿着呈现左旋扭曲。TTR 10 -19原纤维的亚结构不能通过原子力显微镜解析，并且它们的均匀外观暗示了非常细的细丝的规则自缔合。我们提出，淀粉样蛋白原纤维内的原丝的确切数量和方向是由包装的多肽链的区域，不直接参与形成的交叉β核心的原纤维。这些蛋白质与任何人类疾病都没有直接关系，其结果与疾病相关的淀粉样蛋白原纤维非常相似，支持淀粉样蛋白是多肽链的一般结构的概念。然而，单个原纤维的详细结构取决于原丝组装成原纤维结构的方式，而原丝组装成原纤维结构的方式又取决于多肽的序列和原纤维形成的条件。
Atomic force microscopy has been employed to investigate the structural organization of amyloid fibrils produced in vitro from three very different polypeptide sequences. The systems investigated are a 10-residue peptide derived from the sequence of transthyretin, the 90-residue SH3 domain of bovine phosphatidylinositol-3'-kinase, and human wild-type lysozyme, a 130-residue protein containing four disulfide bridges. The results demonstrate distinct similarities between the structures formed by the different classes of fibrils despite the contrasting nature of the polypeptide species involved. SH3 and lysozyme fibrils consist typically of four protofilaments, exhibiting a left-handed twist along the fibril axis. The substructure of TTR10-19 fibrils is not resolved by atomic force microscopy and their uniform appearance is suggestive of a regular self-association of very thin filaments. We propose that the exact number and orientation of protofilaments within amyloid fibrils is dictated by packing of the regions of the polypeptide chains that are not directly involved in formation of the cross-beta core of the fibrils. The results obtained for these proteins, none of which is directly associated with any human disease, are closely similar to those of disease-related amyloid fibrils, supporting the concept that amyloid is a generic structure of polypeptide chains. The detailed architecture of an individual fibril, however, depends on the manner in which the protofilaments assemble into the fibrillar structure, which in turn is dependent on the sequence of the polypeptide and the conditions under which the fibril is formed.