Unfolding the Mysteries of Protein Metamorphosis.

Unfolding the Mysteries of Protein Metamorphosis.
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DOI:
10.1021/acschembio.8b00276
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发表时间:
2018-06-15
影响因子:
4
通讯作者:
Volkman BF
Volkman BF
中科院分区:
生物学2区
文献类型:
--
作者:
Dishman AF;Volkman BF

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自1963年Anfinsen提出热力学假说以来,我们对蛋白质折叠和动力学的理解已经对其细微差别和复杂性有了显著的认识。内部无序蛋白、变色龙序列、morpheein和变态蛋白拓宽了蛋白质折叠的范例。在这里,我们讨论非经典蛋白质的折叠模式,重点是变态蛋白质,我们回顾已知的自然发生的变态蛋白质,并已在实验室工程。最后,我们讨论了围绕变质蛋白质的研究领域,这些蛋白质为未来的探索做好了准备,包括进化、药物发现和对以前未被认识的变质蛋白的探索。随着我们进入一个能够进行复杂的生物信息学搜索和从头设计蛋白质的时代,我们已经准备好寻找以前未被识别的变形蛋白质,并设计我们自己的变形蛋白质作为靶向的、可转换的药物、生物传感器等等。
Since the proposal of Anfinsen’s thermodynamic hypothesis in 1963, our understanding of protein folding and dynamics has gained significant appreciation of its nuance and complexity. Intrinsically disordered proteins, chameleonic sequences, morpheeins, and metamorphic proteins have broadened the protein folding paradigm. Here, we discuss noncanonical protein folding patterns, with an emphasis on metamorphic proteins, and we review known metamorphic proteins that occur naturally and that have been engineered in the laboratory. Finally, we discuss research areas surrounding metamorphic proteins that are primed for future exploration, including evolution, drug discovery, and the quest for previously unrecognized metamorphs. As we enter an age where we are capable of complex bioinformatic searches and de novo protein design, we are primed to search for previously unrecognized metamorphic proteins and to design our own metamorphs to act as targeted, switchable drugs; biosensors; and more.
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