Molecular structure of amyloid fibrils formed by residues 127 to 147 of the human prion protein.
Molecular structure of amyloid fibrils formed by residues 127 to 147 of the human prion protein.
复制标题
DOI：
10.1002/chem.200903290
复制
发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Ni-Shian Lin;John Chin Hao Chao;Hsin-Mei Cheng;Fang-Chieh Chou;Chi-Fon Chang;Yun-Ru Chen;Yu-Jen Chang;Shing‐Jong Huang;J. Chan
中科院分区：
文献类型：
--
作者：
Ni-Shian Lin;John Chin Hao Chao;Hsin-Mei Cheng;Fang-Chieh Chou;Chi-Fon Chang;Yun-Ru Chen;Yu-Jen Chang;Shing‐Jong Huang;J. Chan
淀粉样原纤维是肽或蛋白质的丝状且不溶形式。长期以来，脯氨酸一直被认为与淀粉样原纤维的交叉β结构基序不相容。基于固态核磁共振波谱数据，我们提出了由人类朊病毒蛋白片段 huPrP(127-47) 形成的淀粉样蛋白原纤维的对准平行 β 片层的结构模型。我们开发了一种简单的固态核磁共振波谱技术，可在 H/D 交换实验中识别溶剂保护的主链酰胺质子，而不分解淀粉样原纤维，从中我们发现脯氨酸残基 P(137) 不会破坏从 G(127) 到 G(142) 的 β 折叠结构。我们认为 P(137) 处产生的扭结会在相邻肽链之间产生扭曲，以维持 P(137) 残基侧翼的 β 折叠区域中的氢键结合。虽然脯氨酸可以很好地整合到淀粉样蛋白原纤维的交叉β结构中，但在脯氨酸残基位置形成的扭结将大大削弱相邻链之间的氢键，特别是当突变位点靠近β折叠的中心区域时。
Amyloid fibrils are filamentous and insoluble forms of peptides or proteins. Proline has long been considered to be incompatible with the cross-beta structural motif of amyloid fibrils. On the basis of solid-state NMR spectroscopy data, we present a structural model of an in-register parallel beta sheet for the amyloid fibrils formed from a human prion protein fragment, huPrP(127-47). We have developed a simple solid-state NMR spectroscopy technique to identify solvent-protected backbone amide protons in a H/D exchange experiment without disaggregating the amyloid fibrils, from which we find that proline residue P(137) does not disrupt the beta-sheet structure from G(127) to G(142). We suggest that the resultant kink at P(137) generates a twist between adjacent peptide strands to maintain hydrogen bonding in the beta-sheet regions flanking the P(137) residue. Although proline can be well integrated into the cross-beta structure of amyloid fibrils, the kink formed at the position of the proline residue will considerably weaken the hydrogen bonding between the neighboring strands, especially when the mutation site is near the central region of a beta sheet.