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Creation of artificial protein–protein interactions using α-helices as interfaces

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Abstract

Designing novel protein–protein interactions (PPIs) with high affinity is a challenging task. Directed evolution, a combination of randomization of the gene for the protein of interest and selection using a display technique, is one of the most powerful tools for producing a protein binder. However, the selected proteins often bind to the target protein at an undesired surface. More problematically, some selected proteins bind to their targets even though they are unfolded. Current state-of-the-art computational design methods have successfully created novel protein binders. These computational methods have optimized the non-covalent interactions at interfaces and thus produced artificial protein complexes. However, to date there are only a limited number of successful examples of computationally designed de novo PPIs. De novo design of coiled-coil proteins has been extensively performed and, therefore, a large amount of knowledge of the sequence–structure relationship of coiled-coil proteins has been accumulated. Taking advantage of this knowledge, de novo design of inter-helical interactions has been used to produce artificial PPIs. Here, we review recent progress in the in silico design and rational design of de novo PPIs and the use of α-helices as interfaces.

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Acknowledgements

The work was supported by JSPS KAKENHI Grant Number 16K14494 to S.A. and by MEXT-Supported Program for the Strategic Research Foundation at Private Universities (S1512002), 2015–2017 to A.Y.

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  1. Department of Applied Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Sota Yagi & Akihiko Yamagishi

  2. Faculty of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama, 359-1192, Japan

    Satoshi Akanuma

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  1. Sota Yagi
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Sota Yagi declares that he has no conflicts of interest. Satoshi Akanuma declares that he has no conflicts of interest. Akihiko Yamagishi declares that he has no conflicts of interest.

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This article is part of a Special Issue on ‘Biomolecules to Bio-nanomachines—Fumio Arisaka 70th Birthday’ edited by Damien Hall, Junichi Takagi and Haruki Nakamura.

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Yagi, S., Akanuma, S. & Yamagishi, A. Creation of artificial protein–protein interactions using α-helices as interfaces. Biophys Rev 10, 411–420 (2018). https://doi.org/10.1007/s12551-017-0352-9

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