Liang Chungwen, Derreumaux Philippe, Wei Guanghong
National Key Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai, China.
Biophys J. 2007 Nov 15;93(10):3353-62. doi: 10.1529/biophysj.107.105585. Epub 2007 Aug 10.
Many human neurodegenerative diseases are associated with amyloid fibril formation. The human 99-residue beta(2)-microglobulin (beta2m) is one of the most intensively studied amyloid-forming proteins. Recent studies show that the C-terminal fragments 72-99, 83-89, and 91-96 form by themselves amyloid fibrils in vitro and play a significant role in fibrillization of the full-length beta2m protein under acidic pH conditions. In this work, we have studied the equilibrium structures of the 17-residue fragment 83-99 in solution, and investigated its dimerization process by multiple molecular dynamics simulations. We find that an intertwined dimer, with the positions of the beta-strands consistent with the results for the monomer, is a possible structure for two beta2m(83-89) peptides. Based on our molecular-dynamics-generated dimeric structure, a protofibril model is proposed for the full-length beta2m protein.
许多人类神经退行性疾病都与淀粉样纤维的形成有关。人类99个残基的β2-微球蛋白（β2m）是研究最深入的淀粉样蛋白形成蛋白之一。最近的研究表明，C末端片段72-99、83-89和91-96在体外自身形成淀粉样纤维，并在酸性pH条件下全长β2m蛋白的纤维化过程中起重要作用。在这项工作中，我们研究了溶液中17个残基片段83-99的平衡结构，并通过多次分子动力学模拟研究了其二聚化过程。我们发现，一种相互缠绕的二聚体，其β链的位置与单体的结果一致，是两个β2m(83-89)肽的一种可能结构。基于我们分子动力学生成的二聚体结构，提出了全长β2m蛋白的原纤维模型。
