Molecular conformation of a peptide fragment of transthyretin in an amyloid fibril
Molecular conformation of a peptide fragment of transthyretin in an amyloid fibril
复制标题
DOI：
10.1073/pnas.252625999
复制
发表时间：
2002-12-24
影响因子：
11.1
通讯作者：
Griffin, RG
中科院分区：
文献类型：
--
作者：
Jaroniec, CP;MacPhee, CE;Griffin, RG
用魔角旋转固体核磁共振波谱测定了转甲状腺蛋白TTR(105-115)的多肽片段105-115的分子构象，该片段在体外可形成淀粉样纤维。C-13和N-15线宽测量表明，TTR(105-115)在独特的环境中与每个氨基酸形成高度有序的结构。2D(CC)-C-13-C-13和N-15-C-13-C-13化学位移相关实验，在连续4个氨基酸的连续伸展上均匀地标记了C-13，N-15-C-13，使105-114残基获得了完整的序列特异性主链和侧链C-13和N-15共振指定。通过对N-15、(CO)-C-13、C-13(α)和C-13(β)化学位移的分析，可以对主干扭转角Phi和psi进行定量预测。此外，用旋转回波双共振核磁共振仪测定了两个选择性标记C-13，N-15的纤维样品中的四个主链C-13-N-15距离。结果表明，TTR(105-115)采用了与天然蛋白质相似的扩展的β-链构象，只是在Pro残基附近有很大的不同。
The molecular conformation of peptide fragment 105-115 of transthyretin, TTR(105-115), previously shown to form amyloid fibrils in vitro, has been determined by magic-angle spinning solid-state NMR spectroscopy. C-13 and N-15 linewidth measurements indicate that TTR(105-115) forms a highly ordered structure with each amino acid in a unique environment. 2D (CC)-C-13-C-13 and N-15-C-13-C-13 chemical shift correlation experiments, performed on three fibril samples uniformly C-13,N-15-labeled in consecutive stretches of 4 aa, allowed the complete sequence-specific backbone and side-chain C-13 and N-15 resonance assignments to be obtained for residues 105-114. Analysis of the N-15, (CO)-C-13, C-13(alpha), and C-13(beta) chemical shifts allowed quantitative predictions to be made for the backbone torsion angles phi and psi. Furthermore, four backbone C-13-N-15 distances were determined in two selectively C-13,N-15-labeled fibril samples by using rotational-echo double-resonance NMR. The results show that TTR(105-115) adopts an extended beta-strand conformation that is similar to that found in the native protein except for substantial differences in the vicinity of the proline residue.