Briknarová Klára, Akerman Maria E, Hoyt David W, Ruoslahti Erkki, Ely Kathryn R
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037-1062, USA.
J Mol Biol. 2003 Sep 5;332(1):205-15. doi: 10.1016/s0022-2836(03)00890-8.
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.
Anastellin是人类纤连蛋白第一个FN3结构域的羧基末端片段。它能够在体外使纤连蛋白聚合，并且在体内表现出抗肿瘤、抗转移和抗血管生成特性。我们利用核磁共振光谱法确定了Anastellin的结构，并鉴定出对其活性至关重要的残基。Anastellin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结构域的相应区域非常相似。然而，其疏水核心变得可与溶剂接触，并且其一些β链失去了对来自其他分子的β链氢键作用的保护。这些特征似乎与Anastellin的纤连蛋白聚合活性相关，并且类似于淀粉样原纤维前体的特征。我们认为这种相似性并非偶然，可能反映了纤连蛋白和淀粉样原纤维形成之间的相似性。
