Inter-cofactor protein remodeling rewires short-circuited transmembrane electron transfer

Abstract Intraprotein electron transfer (ET) requires explicit local control of the environment of cofactors to influence their intermolecular distances, relative orientations, and redox properties. Efficient, longer-range ET often utilizes molecular orbitals of aromatic residues present in the inte...

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Main Authors: Deborah K. Hanson, James C. Buhrmaster, Ryan M. Wyllie, Gregory A. Tira, Kaitlyn M. Faries, Dewey Holten, Christine Kirmaier, Philip D. Laible
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Communications Chemistry
Online Access:https://doi.org/10.1038/s42004-025-01460-y
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Summary:Abstract Intraprotein electron transfer (ET) requires explicit local control of the environment of cofactors to influence their intermolecular distances, relative orientations, and redox properties. Efficient, longer-range ET often utilizes molecular orbitals of aromatic residues present in the intervening space. Here, revitalization of a vestigial ET pathway in the bacterial photosynthetic reaction center is achieved by scanning with tryptophans to uncover markedly improved routes of electron conduction in a key stabilizing step spanning 15 Å between tetrapyrrole and quinone cofactors. This ET event is maximally enhanced by pairing one or more tryptophans with a threonine to influence quinone binding and/or redox potential. Synergistic effects of these substitutions increase the yield of that ET step to ~95%. Joining these substitutions with mutant residues that improve initial ET steps dramatically enhances transmembrane charge separation via this redesigned version of a pathway that is quantitatively inactive in the native protein-cofactor complex.
ISSN:2399-3669