Identification of multiple amyloidogenic sequences in laminin-1
Identification of multiple amyloidogenic sequences in laminin-1
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DOI：
10.1021/bi062097t
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发表时间：
2007-04-03
期刊：
影响因子：
2.9
通讯作者：
Nomizu, Motoyoshi
中科院分区：
文献类型：
--
作者：
Kasai, Shingo;Urushibata, Shunsuke;Nomizu, Motoyoshi
淀粉样原纤维的形成与多种病理有关，包括阿尔茨海默病、帕金森病、II 型糖尿病和朊病毒病。最近，报道了基底膜成分与淀粉样蛋白沉积之间的关系。基底膜蛋白层粘连蛋白可能与淀粉样蛋白相关疾病有关，因为层粘连蛋白存在于阿尔茨海默病的淀粉样蛋白斑中并与淀粉样蛋白前体蛋白结合。最近，我们发现肽 A208 (AASIKVAVSADR)（含有 IKVAV 的肽）可形成淀粉样蛋白样原纤维。我们之前使用总共 673 个 12 聚体合成肽鉴定了 laminin-1 中的 60 个细胞粘附序列。在这里，我们从层粘连蛋白-1 衍生的 60 个细胞粘附肽中筛选了额外的淀粉样蛋白生成序列。我们首先检查了 60 种活性肽与刚果红（一种与许多淀粉样蛋白结合的组织学染料）形成的淀粉样蛋白原纤维。十三种肽用刚果红染色。 13 种肽中的 4 种与含有 IKVAV 的肽一样，可促进细胞附着和神经突生长。在 X 射线衍射和电子显微镜分析中，这四种肽还显示出类淀粉样原纤维的形成。淀粉样肽含有共有氨基酸成分，包括碱性和酸性氨基酸以及丝氨酸和异亮氨酸残基。这些结果表明至少五种层粘连蛋白衍生肽可以形成淀粉样蛋白样原纤维。我们得出的结论是，层粘连蛋白衍生的淀粉样蛋白生成肽有可能在体内形成淀粉样蛋白样原纤维，这可能是在层粘连蛋白-1 被降解时发生的。
Amyloid fibril formation is associated with several pathologies, including Alzheimer's disease, Parkinson's disease, type II diabetes, and prion diseases. Recently, a relationship between basement membrane components and amyloid deposits has been reported. The basement membrane protein, laminin, may be involved in amyloid-related diseases, since laminin is present in amyloid plaques in Alzheimer's disease and binds to amyloid precursor protein. Recently, we showed that peptide A208 (AASIKVAVSADR), the IKVAV-containing peptide, formed amyloid-like fibrils. We previously identified 60 cell adhesive sequences in laminin-1 using a total of 673 12-mer synthetic peptides. Here, we screened for additional amyloidogenic sequences among 60 cell adhesive peptides derived from laminin-1. We first examined amyloid-like fibril formation by the 60 active peptides with Congo red, a histological dye binding to many amyloid-like proteins. Thirteen peptides were stained with Congo red. Four of the 13 peptides promoted cell attachment and neurite outgrowth like the IKVAV-containing peptide. The four peptides also showed amyloid-like fibril formation in both X-ray diffraction and electron microscopic analyses. The amyloidogenic peptides contain consensus amino acid components, including both basic and acidic amino acids and Ser and Ile residues. These results indicate that at least five laminin-derived peptides can form amyloid-like fibrils. We conclude that the laminin-derived amyloidogenic peptides have the potential to form amyloid-like fibrils in vivo, possibly when laminin-1 is degraded.