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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Molecular basis for insulin fibril assembly
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Molecular basis for insulin fibril assembly

机译：胰岛素原纤维组装的分子基础

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摘要

In the rare medical condition termed injection amyloidosis, extracellular fibrils of insulin are observed. We found that the segment of the insulin B-chain with sequence LVEALYL is the smallest segment that both nucleates and inhibits the fibrillation of full-length insulin in a molar ratio-dependent manner, suggesting that this segment is central to the cross-β spine of the insulin fibril. In isolation from the rest of the protein, LVEALYL forms microcrys-talline aggregates with fibrillar morphology, the structure of which we determined to 1 A resolution. The LVEALYL segments are stacked into pairs of tightly interdigitated β-sheets, each pair displaying the dry steric zipper interface typical of amyloid-like fibrils. This structure leads to a model for fibrils of human insulin consistent with electron microscopic, x-ray fiber diffraction, and biochemical studies.
机译：在称为注射淀粉样变性的罕见医学病状中，观察到胰岛素的细胞外原纤维。我们发现，具有序列LVEALYL的胰岛素B链片段是最小的片段，该片段以摩尔比依赖性方式既成核又抑制全长胰岛素的原纤维形成，这表明该片段是交叉β脊柱的核心胰岛素原纤维。与蛋白质的其余部分分离，LVEALYL形成具有纤维状形态的微晶-talline聚集体，我们确定其结构为1 A分辨率。 LVEALYL片段被堆叠成成对的紧密相互交叉的β片，每对都显示出淀粉样蛋白原纤维典型的干燥空间拉链界面。这种结构产生了与电子显微镜，X射线纤维衍射和生化研究一致的人胰岛素原纤维模型。

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    Magdalena I. Ivanova; Stuart A. Sievers; Michael R. Sawaya; Joseph S. Wall; David Eisenberg;

  • 作者单位

    Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Los Angeles CA 90095-1570;

    Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Los Angeles CA 90095-1570;

    Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Los Angeles CA 90095-1570;

    Biology Department, Brookhaven National Laboratory, Upton, NY 11973-5000;

    Howard Hughes Medical Institute, UCLA-DOE Institute for Genomics and Proteomics, Los Angeles CA 90095-1570;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    amyloid; fibril structure;

    机译：淀粉样蛋白原纤维结构;

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