Conformational flexibility of the nitrogenase-like reductase CfbC/D involved in coenzyme F430 biosynthesis
4 affiliations
- 1Institut für Biochemie, Fakultät für Chemie und Pharmazie, Albert-Ludwigs-Universität Freiburg, Freiburg 79104, Germany
- 2Faculty of Synthetic Biology and Institute of Emerging Agricultural Technology, Shenzhen University of Advanced Technology, Shenzhen 518107, China
- 3Institut für Pharmazeutische Wissenschaften, Fakultät für Chemie und Pharmazie, Albert-Ludwigs-Universität Freiburg, Freiburg 79104, Germany
- 4Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg 79104, Germany
Abstract
The nitrogenase-like reductase CfbC/D catalyzes the six-electron reduction of the tetrapyrrole macrocycle of Ni2+-sirohydrochlorin a,c-diamide during the biosynthesis of coenzyme F430, an essential cofactor for biological methane formation and consumption. The individual dimeric protein components, CfbC2 and CfbD2, form a complex to allow for electron transfer from the [4Fe:4S] cluster in CfbC2 to the [4Fe:4S] cluster in CfbD2 and onto the substrate. The overall process is ATP-dependent. Although CfbC/D belongs to the family of nitrogenase-like enzymes, there are several intriguing differences between CfbC/D, other nitrogenase-like enzymes and nitrogenase itself. In contrast to the other enzymes, CfbC/D exhibits a simpler molecular architecture, forming a heterotetrameric CfbC2D2 assembly. Furthermore, the interaction of the CfbC and CfbD components does not depend on the presence of adenosine triphosphate (ATP). Here we report cryoelectron microscopy structures of the CfbC/D complex prepared in the absence and presence of substrates. These structures not only shed light on the molecular architecture of the CfbC/D complex but also reveal a high degree of structural flexibility within the CfbD2 component, which undergoes a large conformational change in the presence of an ATP analog and the tetrapyrrole substrate. The interplay of CfbD with its reductase CfbC also strongly suggests an evolutionary pathway toward the modern nitrogenase from methanogenic archaea.
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BibTeX
@article{zhang2026conformational,
title = {{Conformational flexibility of the nitrogenase-like reductase CfbC/D involved in coenzyme F430 biosynthesis}},
author = {Lin Zhang and Florian Schuhmacher and Alena Kussler and Oliver Einsle and Gunhild Layer},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2611794123},
url = {https://doi.org/10.1073/pnas.2611794123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Conformational flexibility of the nitrogenase-like reductase CfbC/D involved in coenzyme F430 biosynthesis
AU - Lin Zhang
AU - Florian Schuhmacher
AU - Alena Kussler
AU - Oliver Einsle
AU - Gunhild Layer
PY - 2026
DA - 2026/10/20
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2611794123
UR - https://doi.org/10.1073/pnas.2611794123
AB - The nitrogenase-like reductase CfbC/D catalyzes the six-electron reduction of the tetrapyrrole macrocycle of Ni2+-sirohydrochlorin a,c-diamide during the biosynthesis of coenzyme F430, an essential cofactor for biological methane formation and consumption. The individual dimeric protein components, CfbC2 and CfbD2, form a complex to allow for electron transfer from the [4Fe:4S] cluster in CfbC2 to the [4Fe:4S] cluster in CfbD2 and onto the substrate. The overall process is ATP-dependent. Although CfbC/D belongs to the family of nitrogenase-like enzymes, there are several intriguing differences between CfbC/D, other nitrogenase-like enzymes and nitrogenase itself. In contrast to the other enzymes, CfbC/D exhibits a simpler molecular architecture, forming a heterotetrameric CfbC2D2 assembly. Furthermore, the interaction of the CfbC and CfbD components does not depend on the presence of adenosine triphosphate (ATP). Here we report cryoelectron microscopy structures of the CfbC/D complex prepared in the absence and presence of substrates. These structures not only shed light on the molecular architecture of the CfbC/D complex but also reveal a high degree of structural flexibility within the CfbD2 component, which undergoes a large conformational change in the presence of an ATP analog and the tetrapyrrole substrate. The interplay of CfbD with its reductase CfbC also strongly suggests an evolutionary pathway toward the modern nitrogenase from methanogenic archaea.
SN - 0027-8424
SN - 1091-6490
ER -