Document Type
Article
Publication Date
4-2025
Publisher
Nature Publishing
Source Publication
Nature Communications
Source ISSN
2041-1723
Original Item ID
DOI: 10.1038/s41467-025-59158-7
Abstract
Enzymes that catalyze long-range electron transfer (ET) reactions often function as higher order complexes that possess two structurally symmetrical halves. The functional advantages for such an architecture remain a mystery. Using cryoelectron microscopy we capture snapshots of the nitrogenase-like dark-operative protochlorophyllide oxidoreductase (DPOR) during substrate binding and turnover. DPOR catalyzes reduction of the C17 = C18 double bond in protochlorophyllide during the dark chlorophyll biosynthetic pathway. DPOR is composed of electron donor (L-protein) and acceptor (NB-protein) component proteins that transiently form a complex in the presence of ATP to facilitate ET. NB-protein is an α2β2 heterotetramer with two structurally identical halves. However, our structures reveal that NB-protein becomes functionally asymmetric upon substrate binding. Asymmetry results in allosteric inhibition of L-protein engagement and ET in one half. Residues that form a conduit for ET are aligned in one half while misaligned in the other. An ATP hydrolysis-coupled conformational switch is triggered once ET is accomplished in one half. These structural changes are then relayed to the other half through a di-nuclear copper center at the tetrameric interface of the NB-protein and leads to activation of ET and substrate reduction. These findings provide a mechanistic blueprint for regulation of long-range electron transfer reactions.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Kashyap, Rajnandani; Walsh, Natalie; Deveryshetty, Jaigeeth; Tokmina-Lukaszewska, Monika; Zhao, Kewei; Gan, Yunqiao J.; Hoffman, Brian M.; Sarangi, Ritimukta; Bothner, Brian; Bennett, Brian; and Antony, Edwin, "Cryo-EM Captures the Coordination of Asymmetric Electron Transfer Through a Di-Copper Site in DPOR" (2025). Physics Faculty Research and Publications. 193.
https://epublications.marquette.edu/physics_fac/193
Comments
Published version. Nature Communications, Vol. 16, No. 1 (April 2025): 3866. DOI. © The Author(s) 2025. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by-nc-nd/4.0/.