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体外进化从头产生随机序列的蛋白质。

De novo proteins from random sequences through in vitro evolution.

机构信息

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA; BioTechnology Institute, University of Minnesota, St. Paul, MN, USA.

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA; BioTechnology Institute, University of Minnesota, St. Paul, MN, USA.

出版信息

Curr Opin Struct Biol. 2021 Jun;68:129-134. doi: 10.1016/j.sbi.2020.12.014. Epub 2021 Jan 28.

Abstract

Natural proteins are the result of billions of years of evolution. The earliest predecessors of today's proteins are believed to have emerged from random polypeptides. While we have no means to determine how this process exactly happened, there is great interest in understanding how it reasonably could have happened. We are reviewing how researchers have utilized in vitro selection and molecular evolution methods to investigate plausible scenarios for the emergence of early functional proteins. The studies range from analyzing general properties and structural features of unevolved random polypeptides to isolating de novo proteins with specific functions from synthetic randomized sequence libraries or generating novel proteins by combining evolution with rational design. While the results are exciting, more work is needed to fully unravel the mechanisms that seeded protein-dominated biology.

摘要

天然蛋白质是数十亿年进化的结果。今天蛋白质的最早前身被认为是从随机多肽中产生的。虽然我们无法确定这个过程到底是如何发生的,但人们非常有兴趣了解它是如何合理发生的。我们正在回顾研究人员如何利用体外选择和分子进化方法来研究早期功能蛋白质出现的合理情况。这些研究从分析未进化的随机多肽的一般性质和结构特征,到从合成随机序列文库中分离具有特定功能的从头蛋白质,或通过将进化与合理设计相结合生成新的蛋白质,不一而足。虽然结果令人兴奋,但要完全揭示引发以蛋白质为主导的生物学的机制,还需要做更多的工作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c72c/8222087/f6d816ea2d84/nihms-1668074-f0001.jpg

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De novo proteins from random sequences through in vitro evolution.体外进化从头产生随机序列的蛋白质。
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A Completely ATPase from Combinatorial Protein Design.组合蛋白设计的完全 ATP 酶。
J Am Chem Soc. 2020 Sep 9;142(36):15230-15234. doi: 10.1021/jacs.0c02954. Epub 2020 Aug 31.
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On the evolution of protein-adenine binding.关于蛋白质-腺嘌呤结合的演变。
Proc Natl Acad Sci U S A. 2020 Mar 3;117(9):4701-4709. doi: 10.1073/pnas.1911349117. Epub 2020 Feb 20.
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protein design, a retrospective.蛋白质设计:回顾
Q Rev Biophys. 2020 Feb 11;53:e3. doi: 10.1017/S0033583519000131.
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Selection of Peptides and Proteins-Advantages of mRNA Display.肽和蛋白质的选择——mRNA 展示的优势。
ACS Synth Biol. 2020 Feb 21;9(2):181-190. doi: 10.1021/acssynbio.9b00419. Epub 2020 Jan 14.
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Are natural proteins special? Can we do that?天然蛋白质特殊吗?我们能做到吗?
Curr Opin Struct Biol. 2018 Feb;48:124-132. doi: 10.1016/j.sbi.2017.11.009. Epub 2018 Jan 3.

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