Structure of the ATP-driven Methyl-coenzyme M reductase activation complex
Fidel Ramírez-Amador#, Sophia Paul#, Anuj Kumar#, Christian Lorent, Sebastian Keller, Stefan Bohn, Thinh Nguyen, Stefano Lometto, Dennis Vlegels, Jörg Kahnt, Darja Deobald, Frank Abendroth, Olalla Vázquez, Georg Hochberg, Silvan Scheller, Sven Stripp, Jan M. Schuller*
Nature 2025
We combined redox-controlled cryoEM with biochemical, spectroscopic and phylogenetic evidence to report on the central machinery that activates Methyl-coenzyme M reductase (MCR) - one of the most abundant enzymes on Earth and the major biological producer of methane. The strict ATP-dependency to reduce coenzyme F430 as well as an unprecedented electron-transfer pathway composed of nitrogenase-like cofactors are described for this ancient bioenergetic system.
Molecular principles of redox-coupled sodium pumping of the ancient Rnf machinery
Anuj Kumar#, Jennifer Roth#, Hyunho Kim#, Patricia Saura#, Stefan Bohn, Tristan Reif-Trauttmansdorff, Anja Schubert, Ville R. I. Kaila*, Jan M. Schuller*, Volker Müller*
Nature communications 2025
We show the cryoEM structure of the Rnf complex - the ancient primary respiratory enzyme of several anaerobic prokaryotes - providing evidence on its mechanism for redox-driven ion pumping, one of the key fundamental principles governing energy conversion in biological systems.
Emergence of fractal geometries in the evolution of a metabolic enzyme
Franziska L. Sendker, Yat Kei Lo, Thomas Heimerl, Stefan Bohn, Louise J. Persson, Christopher-Nils Mais, Wiktoria Sadowska, Nicole Paczia, Eva Nußbaum, María del Carmen Sánchez Olmos, Karl Forchhammer, Daniel Schindler, Tobias J. Erb, Justin L. P. Benesch, Erik G. Marklund, Gert Bange, Jan M. Schuller*, Georg K. A. Hochberg*
Nature 2024
A cyanobacterium enzyme that spontaneously assembles into a pattern known as the Sierpinski triangle. CryoEM and ancestral sequence reconstruction studies indicate that this fractal - the first molecular assembly of its kind that is found in nature - may represent an evolutionary accident.
Frequent transitions in self-assembly across the evolution of a central metabolic enzyme
Franziska L. Sendker, Tabea Schlotthauer, Christopher-Nils Mais, Yat Kei Lo, Mathias Girbig, Stefan Bohn, Thomas Heimerl, Daniel Schindler, Arielle Weinstein, Brian P. H. Metzger, Joseph W. Thornton, Arvind Pillai, Gert Bange, Jan M. Schuller, Georg K. A. Hochberg*
Nature communications 2024
This work suggests that enzymes can wander relatively freely through a large space of possible assembly states and demonstrates the power of characterizing structure-function relationships across entire phylogenies.
Molecular architecture and electron transfer pathway of the Stn family transhydrogenase
Anuj Kumar#, Florian Kemp#, Jennifer Roth, Sven A. Freibert, Volker Müller*, Jan M. Schuller*
Nature communications 2023
We present the cryoEM structure of the Stn complex from an acetogenic bacterium. By dissecting its electron transfer pathway, we demonstrate that Stn holds subunits with the structural and funcional role of electron bifurcation, homologous to the electron-bifurcating core of our previously reported hydrogenase complex HydABC.
2-oxoglutarate triggers assembly of active dodecameric Methanosarcina mazei glutamine synthetase
Eva Herdering#, Tristan Reif-Trauttmansdorff#, Anuj Kumar, Tim Habenicht, Georg Hochberg, Stefan Bohn, Jan M. Schuller*, Ruth Anne Schmitz*
eLife 2025
We investigated how 2-oxoglutarate (2-OG) strongly activates the glutamine synthetase from M. mazei by the 2-OG dependent dodecamer assembly of GlnA1. By coupling mass photometry and single particle cryo-EM with activity assays, we evaluated the complex formation of GlnA1 with the small proteins GlnK1 and sP26.
A bacterial W-containing aldehyde oxidoreductase forms an enzymatic decorated protein nanowire
Agnieszka Winiarska#, Fidel Ramírez-Amador#, Dominik Hege, Yvonne Gemmecker, Simone Prinz, Georg Hochberg, Johann Heider*, Maciej Szaleniec*, Jan M. Schuller*
Science Advances 2023
This fantastic aldehyde oxidoreductase does not only oxidize a high spectrum of aldehydes or performs the thermodinamically difficult opposite reaction, but it also forms filaments in a similar fashion as the previously reported HDCR.
Molecular Basis of the Electron Bifurcation Mechanism in the [FeFe]-Hydrogenase Complex HydABC
Alexander Katsyv#, Anuj Kumar#, Patricia Saura#, Maximilian C. Pöverlein, Sven A. Freibert, Sven T. Stripp, Surbhi Jain, Ana P. Gamiz-Hernandez, Ville R. I. Kaila*, Volker Müller*, Jan M. Schuller*
JACS 2023
In acetogens, the electron bifurcating hydrogenase generates low potential ferredoxin for respiration and CO2 fixation in a way that differs from classical flavin-based electron-bifurcating enzymes (FBEB). After a tremendous effort with our collaborators, we validated this novel mechanism by redox-controlled cryoEM reconstructions, molecular simulations and spectroscopy experiments.
Evolution of increased complexity and specificity at the dawn of form I Rubiscos
Luca Schulz, Zhijun Guo, Jan Zarzycki, Wieland Steinchen, Jan M. Schuller, Thomas Heimerl, Simone Prinz, Oliver Mueller-Cajar, Tobias Erb*, Georg K. A. Hochberg*.
Science 2022
Another exciting colaboration with Tobi and Georg's labs regarding the evolution of Rubisco.
Membrane-anchored HDCR nanowires drive hidrogen-powered CO2 fixation
Helge Dietrich#, Ricardo D. Righetto#, Anuj Kumar, Wojciech Wietrzynski, Raphael Trischler, Sandra K. Schuller, Jonathan Wagner, Fabian M. Schwarz, Benjamin D. Engel*, Volker Müller*, Jan M. Schuller*
Nature 2022
Electron highway for hydrogen and carbon dioxide storage discovered
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Together with researchers from Frankfurt and Basel, we have shed light on the structure of an enzyme that produces formic acid from molecular hydrogen (H2) and carbon dioxide (CO2). The filamentous structure of the enzyme, now described at atomic level for the first time, acts like a nanowire and is evidently responsible for the extremely efficient conversion rates of the two gases. There is no other enzyme reported that converts CO2 to formate with a turnover rate even close to HDCR.
Structure-based electron-confurcation mechanism of the Ldh-EtfAB complex
Kanwal Kayastha, Alexander Katsyv, Christina Himmrich, Sonja Welsch, Jan M. Schuller, Ulrich Ermler*, Volker Müller*
eLife 2022
The first electron-confurcating reaction structurally studied​
A high-resolution cryoEM structure of the lactate dehydrogenase-electron transferring flavoprotein complex (Ldh-EtfAB) from an acetogen was obtained. On this basis, a catalytic mechanism of the flavin-based electron confurcation (FBEC) process has been proposed.
Structural basis for VIPP1 oligomerization and maintenance of thylakoid membrane integrity
Tilak Kumar Gupta#, Sven Klumpe#, Karin Gries#, Steffen Heinz#, Wojciech Wietrzynski#, Norikazu Ohnishi, Justus Niemeyer, Benjamin Spaniol, Miroslava Schaffer, Anna Rast, Matthias Ostermeier, Mike Strauss, Jürgen M. Plitzko, Wolfgang Baumeister, Till Rudack, Wataru Sakamoto, Jörg Nickelsen, Jan M. Schuller*, Michael Schroda*, Benjamin D. Engel*
Cell 2021
The molecular machine that forms the membranes of life!​
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In an amazing 6-lab cooperation we managed to determine the structure and mechanism of the major thylakoid membrane biogenesis factor VIPP1. Our work shows how this green ESCRT-III oligomer mediates membrane remodelling and repair.
Structural insights into photosystem II assembly
Jure Zabret#, Stefan Bohn#, Sandra K Schuller, Oliver Arnolds, Madeline Möller, Jakob Meier-Credo, Pasqual Liauw, Aaron Chan, Emad Tajkhorshid, Julian D Langer, Raphael Stoll, Anja Krieger-Liszkay, Benjamin D Engel, Till Rudack*, Jan M Schuller*, Marc M Nowaczyk*
Nature Plants 2021
How to build a molecular water splitting machine?
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The first structural information on the biogenesis of PSII. We trapped the attachment of the CP43 light harvesting module and determined the high-resolution structure of it. Our work answers how a not yet fully assembled, but already partially active molecular machine is protected from photo damage. Great cooperation with our friends in the Nowaczyk lab. Our future work on this topic is supported by the Walter Benz foundation.
We could contribute the structure of the artifical enzyme glycolyl-CoA carboxylase (GCC), a new-to-nature enzyme to this exciting study by Tobi's lab.
A new-to-nature carboxylation module to improve natural and synthetic CO2 fixation
Marieke Scheffen, Daniel G Marchal, Thomas Beneyton, Sandra K Schuller, Melanie Klose, Christoph Diehl, Jessica Lehmann, Pascal Pfister, Martina Carrillo, Hai He, Selçuk Aslan, Niña S Cortina, Peter Claus, Daniel Bollschweiler, Jean-Christophe Baret, Jan M Schuller, Jan Zarzycki, Arren Bar-Even, Tobias J Erb.
Nature Catalysis 2021
Structural adaptations of photosynthetic complex I enable ferredoxin-dependent electron transfer
Jan M Schuller*, James A Birrell, Hideaki Tanaka, Tsuyoshi Konuma, Hannes Wulfhorst, Nicholas Cox, Sandra K Schuller, Jacqueline Thiemann, Wolfgang Lubitz, Pierre Sétif, Takahisa Ikegami, Benjamin D Engel, Genji Kurisu*, Marc M Nowaczyk*
Science 2019
