A folded and functional protein domain in an amyloid-like fibril
A folded and functional protein domain in an amyloid-like fibril
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DOI：
10.1110/ps.073276308
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发表时间：
2008-06-01
期刊：
影响因子：
8
通讯作者：
Schwarz, Elisabeth
中科院分区：
文献类型：
--
作者：
Sackewitz, Mirko;Von Einem, Sabrina;Schwarz, Elisabeth
利用控制聚腺苷化的核蛋白PAPBN1的淀粉样蛋白片段，研究了多肽环境对聚丙氨酸诱导的原纤维形成的影响。突变引起的天然10个丙氨酸序列延伸至最多17个丙氨酸，导致PABPN1的纤维形成和眼咽肌营养不良症（OPMD）的发展。我们探索了纤维形成对与PABPN1的原纤维形成部分相连的单结构域蛋白的结构和功能的影响。来自枯草芽孢杆菌的冷休克蛋白CspB具有良好的特征，折叠稳定，单结构域，被融合到PABPN1的整个n端结构域的C端或直接融合到由10或17个丙氨酸残基组成的肽上。PABPN1的n端结构域与CspB的融合蛋白形成原纤维，在原纤维中保留了CspB的结构和活性。在多丙氨酸序列与CspB直接相连的融合形成的原纤维中，CspB被展开。这些结果表明，蛋白结构域的折叠构象和功能可以在淀粉样原纤维中维持，并且该结构域与原纤维之间的距离起着重要作用。
The effect of the polypeptide environment on polyalanine-induced fibril formation was investigated with amyloidogenic fragments from PAPBN1, a nuclear protein controlling polyadenylation. Mutation-caused extensions of the natural 10 alanine sequence up to maximally 17 alanines result in fibril formation of PABPN1 and the development of the disease oculopharyngeal muscular dystrophy (OPMD). We explored the influence of fibril formation on the structure and function of a one-domain protein linked to the fibril-forming part of PABPN1. The well-characterized, stably folded, one-domain protein, cold-shock protein CspB from Bacillus subtilis, was fused either to the C terminus of the entire N-terminal domain of PABPN1 or directly to peptides consisting of 10 or 17 alanine residues. The fusion protein between the N-terminal domain of PABPN1 and CspB formed fibrils in which the structure and activity of CspB were retained. In the fibrils formed by fusions in which the polyalanine sequence was directly linked to CspB, CspB was unfolded. These results indicate that the folded conformation and the function of a protein domain can be maintained in amyloid-like fibrils, and that the distance between this domain and the fibril plays an important role.