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27.08.2025 11:52

And yet they move

Dr. Karoline Stürmer Präsidialabteilung, Bereich Kommunikation & Marketing
Universität Regensburg

Researchers reveal the movements of large molecular machines by combining a variety of biophysical techniques

Researchers at the Regensburg Centre for Biochemistry (RCB) and the Regensburg Centre for Ultrafast Nanoscopy (RUN) at the University of Regensburg are obtaining unique insights into the structure, dynamics and function of dynamic components of the exosome, an RNA-degrading molecular machine in the cell. The results not only provide biological information on RNA degradation but are also a methodological milestone in structural elucidation of biomolecules. The work shows that the combination of experimental and computer-assisted biophysical methods facilitates the investigation of dynamics in large molecular machines. Such investigations were not possible before. The interdisciplinary team led by Dr Jobst Liebau, Dr Daniela Lazzaretti, Prof. Dr Till Rudack and Prof. Dr Remco Sprangers reports on their findings in the renowned journal Nature Communications, published online.

Strong together: proteins cooperate
Proteins are the all-rounders in the cells of every living organism and the basis of all life. Often, several proteins form larger complexes that perform a variety of vital tasks as molecular machines. For example, these complexes assemble vital molecules and disassemble them again when they are not needed anymore. Other complexes transport and sort molecules, or they send and receive messages. To understand how those protein complexes perform their functions, one must understand how they look like. In recent decades, researchers have elucidated the three-dimensional (3D) structure of a large number of proteins. The University of Regensburg has its own high-resolution cryo-electron microscope available for this purpose. This microscope was used in the current study to elucidate the static structure of a molecular machine.

Strong together: NMR and MD simulations
‘These structures are very important, but not sufficient,’ says Remco Sprangers, Professor of Biophysics at the University of Regensburg. ‘To truly understand the function of proteins, we need to understand how they move and how their structure changes when they perform their function. This is a task that is even more challenging than elucidating the rigid structure.’ Sprangers' research aims to do just that. Using nuclear magnetic resonance (NMR) spectroscopy, his research group is investigating how proteins change their structure to perform their function. But how can these changes be visualized? NMR data is often very abstract. Molecular dynamics (MD) simulations are used to calculate dynamic structural models that visualize the structural changes. However, these models require experimental verification. ‘The combination of NMR and MD works analogously to a microscope with very high spatial and temporal resolution and provides a kind of movie of the atomic interaction of proteins,’ explains Till Rudack, Professor of Structural Bioinformatics at the University of Regensburg.

Challenge: large molecular machines
In most cases, however, the NMR method only worked for small proteins. ‘NMR often reaches its limits with larger protein complexes. We have now achieved a breakthrough that makes it possible to study the giants of the microscopic world of proteins, such as the RNA exosome complex, which plays a crucial role in RNA degradation,’ explains Jobst Liebau, postdoc in the Sprangers group and first author of the study. ‘In addition, we have now been able to study areas of the exosome complex that were previously invisible to all other methods,’ adds Daniela Lazzaretti, also a postdoc in the Sprangers group.

Dynamic insights into the RNA degradation process
The RNA exosome consists of ten distinct proteins and degrades RNA. This is an essential task in every cell. ‘The fact that we can measure the movements of previously invisible regions allows us to analyze the short-lived interactions between RNA and the exosome,’ explains Jobst Liebau. Some areas of the protein move extremely fast, performing a movement several billion times per second. Other, mostly larger regions move more slowly: ‘only’ 30 times per second. It is precisely these slow movements that often appear to be of central importance for the function of protein complexes. For example, the researchers were able to identify an area in the RNA exosome that moves at roughly the same speed as the exosome degrades RNA. The researchers have not yet been able to prove a direct connection, but without movement, there would be no RNA degradation.

From static to dynamic images
The study thus provides more than a static image. Rather, it provides a kind of movie that offers insights into the dynamic processes of RNA degradation by the exosome complex. ‘Life is movement,’ explains Till Rudack, ‘and the interplay of the NMR method and MD simulations provides deep insights into the dynamic world of proteins.’ ‘The combination of different biophysical methods to elucidate structural dynamics is groundbreaking for future research. We are only just beginning to understand the role that dynamics plays for the function of proteins,’ adds Remco Sprangers. With their study, the researchers have laid the foundation for transforming the previously static images of the microcosm of the cell into moving ones.

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Wissenschaftliche Ansprechpartner:

Prof. Dr. Remco Sprangers
Lehrstuhl für Biophysik
Regensburg Center for Biochemistry
Regensburg Center for Ultrafast Nanoscopy
University of Regensburg
E-Mail: remco.sprangers@ur.de

Prof Dr. Till Rudack
Structural Bioinformatics
Regensburg Center for Biochemistry
Regensburg Center for Ultrafast Nanoscopy
University of Regensburg
E-Mail: till.rudack@ur.de

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Originalpublikation:

doi.org/10.1038/s41467-025-62982-6

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Grafic taken from: Liebau, J., Lazzaretti, D., Fürtges, T. et al. 4D structural biology–quantitative ...

Copyright: Creative Commons Attribution 4.0 International (CC BY 4.0)

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Journalisten, jedermann
Biologie, Medizin, Physik / Astronomie
überregional
Forschungsergebnisse
Englisch

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