Hutchins, George H;
Noble, Claire EM;
Bunzel, H Adrian;
Williams, Christopher;
Dubiel, Paulina;
Yadav, Sathish KN;
Molinaro, Paul M;
... Anderson, JL Ross; + view all
(2023)
An expandable, modular de novo protein platform for precision redox engineering.
Proceedings of the National Academy of Sciences (PNAS)
, 120
(31)
, Article e2306046120. 10.1073/pnas.2306046120.
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Abstract
The electron-conducting circuitry of life represents an as-yet untapped resource of exquisite, nanoscale biomolecular engineering. Here, we report the characterization and structure of a de novo diheme “maquette” protein, 4D2, which we subsequently use to create an expanded, modular platform for heme protein design. A well-folded monoheme variant was created by computational redesign, which was then utilized for the experimental validation of continuum electrostatic redox potential calculations. This demonstrates how fundamental biophysical properties can be predicted and fine-tuned. 4D2 was then extended into a tetraheme helical bundle, representing a 7 nm molecular wire. Despite a molecular weight of only 24 kDa, electron cryomicroscopy illustrated a remarkable level of detail, indicating the positioning of the secondary structure and the heme cofactors. This robust, expressible, highly thermostable and readily designable modular platform presents a valuable resource for redox protein design and the future construction of artificial electron-conducting circuitry.
| Type: | Article |
|---|---|
| Title: | An expandable, modular de novo protein platform for precision redox engineering |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1073/pnas.2306046120 |
| Publisher version: | https://doi.org/10.1073/pnas.2306046120 |
| Language: | English |
| Additional information: | Copyright © 2023 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY), https://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Protein design; bioenergetics; heme proteins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10200355 |
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