De novo proteins from random sequences through in vitro evolution - PubMed (original) (raw)

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De novo proteins from random sequences through in vitro evolution

Cher Ling Tong et al. Curr Opin Struct Biol. 2021 Jun.

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.

Copyright © 2021 Elsevier Ltd. All rights reserved.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1.

Figure 1.

Emergence of de novo proteins from protein sequence space that comprises all possible sequences. (Background image: Hubble space telescope’s view of the milky way (NASA Image and Video Library; URL:

https://images.nasa.gov/details-GSFC\_20171208\_Archive\_e000717

). Protein structure: Protein Data Bank code 5BVL)

Figure 2

Figure 2

3D structures of de novo proteins from random sequences or partly designed randomized sequence libraries. (A) Artificial ATP binding protein [21] (Protein Data Bank code 1UW1). Bound ADP is shown in gray and zinc as a gray sphere. (B) Artificial RNA ligase enzyme [27] (Protein Data Bank code 2LZE). The two highly structured regions (purple) frame the more dynamic loop (black). Flexible termini were omitted for clarity and zinc ions are shown as gray spheres. (C) four-helix bundle protein from a binary-pattern random library [30] (Protein Data Bank code 2JUA). (D) Engineered metalloesterase complexed with a phosphonate transition state analogue (gray) [31] (Protein Data Bank code 5OD1). Zinc is shown as a gray sphere.

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