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An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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设计者蛋白可以触发细胞死亡.

Wayne J Fairbrother1, Avi Ashkenazi2

  • 1Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Cell
|June 21, 2014
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概括
此摘要是机器生成的。

研究人员使用计算方法和有针对性的进化设计了一种新型的多抑制剂. 这种抑制剂有效地向病毒Bcl-2类蛋白质,诱导受感染细胞的亡.

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科学领域:

  • 生物化学 生物化学
  • 计算生物学 计算生物学
  • 分子生物学分子生物学

背景情况:

  • 从历史上看,de novo蛋白质设计一直局限于修改现有的蛋白质支架.
  • 开发针对病毒感染的新型治疗剂仍然是一个关键的挑战.

研究的目的:

  • 通过计算设计和实验验证一种针对病毒BCL-2类蛋白的de novo多抑制剂.
  • 为了研究这种抑制剂在诱导病毒感染细胞的亡中的潜力.

主要方法:

  • 利用一种创新的计算设计策略来创建一种新的蛋白质结构.
  • 在体外向进化中使用,以优化抑制剂的效力和特异性.
  • 评估了抑制剂在病毒感染细胞中触发亡的疗效.

主要成果:

  • 通过新计算设计和有针对性的进化,成功生成了强大的多抑制剂.
  • 设计的抑制剂对类似于Bcl-2的病毒蛋白具有显著的活性.
  • 该抑制剂有效地诱导了病毒感染细胞的亡,突显了其治疗潜力.

结论:

  • 新的计算设计,当与有针对性的进化相结合时,可以产生高效的基于蛋白质的治疗方法.
  • 开发的多抑制剂是通过诱导向细胞死亡来对抗病毒感染的有希望的新策略.