Anastellin, an FN3 fragment with fibronectin polymerization activity, resembles amyloid fibril precursors
Anastellin, an FN3 fragment with fibronectin polymerization activity, resembles amyloid fibril precursors
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DOI：
10.1016/s0022-2836(03)00890-8
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发表时间：
2003-09-05
影响因子：
5.6
通讯作者：
Ely, KR
中科院分区：
文献类型：
--
作者：
Briknarová, K;Åkerman, ME;Ely, KR
Anastellin是人纤维连接蛋白第一个FN3结构域的羧基末端片段。它能在体外聚合纤维连接蛋白，并在体内表现出抗肿瘤、抗转移和抗血管生成的特性。我们用核磁共振波谱法确定了纳氏菌素的结构，并鉴定了对其活性至关重要的残基。青霉素在溶液中表现出动态波动和构象交换。其整体拓扑结构与全长FN3结构域的对应区域非常相似。然而，它的疏水核心变得可溶于溶剂，并且它的一些-链失去了与其他分子的-链形成氢键的保护。这些特征似乎与anastellin的纤维连接蛋白聚合活性有关，并类似于淀粉样纤维前体的特征。我们认为这种类比不是随机的，可能反映了纤维连接蛋白和淀粉样纤维形成之间的相似性。(C) 2003 Elsevier Ltd.版权所有。
Anastellin is a carboxy-terminal fragment of the first FN3 domain from human fibronectin. It is capable of polymerizing fibronectin in vitro, and it displays anti-tumor, anti-metastatic and anti-angiogenic properties in vivo. We have determined the structure of anastellin using nuclear magnetic resonance spectroscopy and identified residues critical for its activity. Anastellin exhibits dynamic fluctuations and conformational exchange in solution. Its overall topology is very similar to the corresponding region of full-length FN3 domains. However, its hydrophobic core becomes solvent-accessible and some of its beta-strands lose their protection against hydrogen bonding to beta-strands from other molecules. These features seem to be relevant for the fibronectin polymerization activity of anastellin and resemble the characteristics of amyloid fibril precursors. We suggest that this analogy is not random and may reflect similarities between fibronectin and amyloid fibril formation. (C) 2003 Elsevier Ltd. All rights reserved.