Biomolecular Mechanisms from Integrated NMR Spectroscopy
Life is in motion. While one immediately realizes the inherently dynamic aspect of living organisms on the macroscopic level, simply by observing it by eye or under a microscope, it is clear that ultimately it is the jiggling and wiggling of the atoms within molecules, and their interactions with each other, that allow life to unfold.
The Schanda group is particularly interested in understanding how biomolecules – primarily proteins – perform their tasks, and how their structural dynamics governs their functions. Their work has several aspects. On the one hand, the group studies a number of puzzling biological questions. For example, how do proteins transport other proteins across the cell, across biological membranes or into membranes? By studying how those proteins – chaperones, receptors, translocases – are structured, how they move and how they interact, they decipher how cells are able to transport large and highly aggregation-prone polypeptides all across the cell and ultimately refold them into their native environment. For example, this work unravels how membrane proteins are getting imported into mitochondria, or how megadalton-large chaperones help other proteins to fold.
On the other hand, the group is interested in somewhat more fundamental physio-chemical aspects of protein dynamics. How do the motions around the active site of an enzyme control its function? And how exactly do the side chains and main chain of proteins move – in solution, in crystals, and in large assemblies? How do protein domains move relative to each other, and does the packing in biological assemblies or crystals impact this motion?
To answer these questions, the Schanda group uses nuclear magnetic resonance (NMR) spectroscopy, which they combine with a host of other biophysical, biochemical, in-silico and in-vivo methods. The integration of these methods, and the further development of NMR methodology is another key interest of the group, as they develop, for example, methodologies that allow solving three-dimensional structures of large proteins or protein complexes from novel NMR experiments, coupled to cryo-EM. Other new NMR methods allow to decipher in great detail how particular parts of proteins move, which then allows linking those motions to function.
The group, thus, spans activities from nuclear spin dynamics and biophysics to challenging biological problems.
On this site:
Everton Dias D’Andrea
Mitochondrial import machinery | Dynamics of enzymatic assemblies | New NMR methods to probe protein dynamics | Integration of NMR with various structural techniques for high-resolution structure determination
Napoli F, Becker LM, Schanda P. 2023. Protein dynamics detected by magic-angle spinning relaxation dispersion NMR. Current Opinion in Structural Biology. 82, 102660. View
Degen M, Santos JC, Pluhackova K, Cebrero G, Ramos S, Jankevicius G, Hartenian E, Guillerm U, Mari SA, Kohl B, Müller DJ, Schanda P, Maier T, Perez C, Sieben C, Broz P, Hiller S. 2023. Structural basis of NINJ1-mediated plasma membrane rupture in cell death. Nature. 618, 1065–1071. View
Troussicot L, Vallet A, Molin M, Burmann BM, Schanda P. 2023. Disulfide-bond-induced structural frustration and dynamic disorder in a peroxiredoxin from MAS NMR. Journal of the American Chemical Society. 145(19), 10700–10711. View
Becker LM, Berbon M, Vallet A, Grelard A, Morvan E, Bardiaux B, Lichtenecker R, Ernst M, Loquet A, Schanda P. 2023. The rigid core and flexible surface of amyloid fibrils probed by Magic‐Angle Spinning NMR of aromatic residues. Angewandte Chemie International Edition. 62(19), e202219314. View
Gauto DF, Lebedenko OO, Becker LM, Ayala I, Lichtenecker R, Skrynnikov NR, Schanda P. 2023. Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD. Journal of Structural Biology: X. 7, 100079. View
ReX-Link: Paul Schanda
Since September 2021 – Professor, Institute of Science and Technology Austria
2017 – 2020 Head of the NMR group, Institut de Biologie Structurale (IBS), Grenoble, FR
2011 – 2021 Research team leader, IBS Grenoble
2008 – 2010 Post-doc, Dept. of Chemistry and Applied Biosciences, ETH Zürich, Switzerland.
2004 – 2007 PhD student, Univ. Joseph Fourier Grenoble (IBS), including research at Weizmann Institute (2005)
2020 Varian Young Investigator Award
2020 ICMRBS Founders’ Medal
2012 ERC StG ProtDyn2Function, 1.5 M€
2010 Young Investigator Award, French Biophysical Society
2008 Post-doc fellowship ‘ETH Fellows’, ETH Zurich (2008)
2004 Boehringer Ingelheim fellowship: competitive and prestigious PhD fellowship