Abstract：
The self-assembly of peptides and proteins into β-sheet rich amyloid fibrils is linked to both functional and pathological states. In this study, the growth of fibrillar structures of the short peptide GNNQQNY, a fragment from the yeast prion Sup35 protein, was examined. Molecular dynamics simulations were used to study alternative mechanisms of fibril growth, including elongation through binding of monomers as well as fibril self-assembly into larger, more mature structures. It was found that after binding, monomers diffused along preformed fibrils toward the ends, supporting the mechanism of fibril growth via elongation. Lateral assembly of protofibrils was found to occur readily, suggesting that this could be the key to transitioning from isolated fibrils to mature multilayer structures. Overall, the work provides mechanistic insights into the competitive pathways that govern amyloid fibril growth.
摘要：
肽和蛋白质自组装成富含β-折叠的淀粉样原纤维与功能和病理状态有关。在这项研究中,短肽GNNQQNY的纤维结构的生长，酵母朊病毒Sup35蛋白的片段，被检查过。分子动力学模拟用于研究原纤维生长的替代机制，包括通过结合单体以及原纤维自组装成更大的伸长，更成熟的结构。发现绑定后，单体沿着预制原纤维向末端扩散，通过伸长支持原纤维生长的机制。发现容易发生原纤维的横向组装，这表明这可能是从分离的原纤维过渡到成熟的多层结构的关键。总的来说,这项工作提供了对控制淀粉样蛋白原纤维生长的竞争途径的机械见解。
