Scientists at the Regensburg Center for Biochemistry (RCB) and the Regensburg Center for Ultrafast Nanoscopy (RUN) are making great progress in deciphering the secrets of exosomes. These ubiquitous RNA-degrading molecular machines are critically important to the dynamic landscape of their cells. Dr. Jobst Liebau, Dr. Daniela Lazzaretti, Prof. Dr. Till Rudack and Prof. Dr. Remco Sprangers head the research team. They combine these imaginative biophysical techniques to unmask the unseen dynamic work that moves and rattles in these beautiful machines.
The exosome, which is a core complex of 10-12 exonuclease subunits, is essential for RNA degradation. This process is extremely important for everyday cellular function, regulation and homeostasis. The team recently published their groundbreaking work in Nature Communications. They found that certain areas of the exosome were hyperdynamic, with motions on the order of billions of times per second, while more macro-scale regions of the motor moved at lower rates, around 30 per second. Further, this research adds to our understanding of RNA degradation more broadly. It yields fascinating insights into the dynamic way proteins work.
Innovative Research Team
The interdisciplinary team includes specialists in crystallography and molecular dynamics simulation, among others, from the fields of biochemistry and biophysics. Prof. Dr. Remco Sprangers is the Chair of Biophysics at University of Regensburg. What’s most significant about their approach, he said.
“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 in the function of proteins.” – Prof. Dr. Remco Sprangers
Dr. Jobst Liebau explains some of the exciting developments that have been enabled by this research.
“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.” – Dr. Jobst Liebau
Dr. Daniela Lazzaretti, a postdoctoral researcher in Sprangers’ group, explains the importance of their work. It has now unlocked doors to learning about parts of the exosome we could never reach before.
“In addition, we have now been able to study areas of the exosome complex that were previously invisible to all other methods.” – Dr. Lazzaretti
Understanding Molecular Dynamics
To understand the structural transitions happening inside the exosome, the researchers use molecular dynamics (MD) simulations. With these simulations they can generate dynamic structural models that render the exosome in action, in real-time.
Prof. Dr. Till Rudack states that their combined methodology offers unprecedented insight:
“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.” – Prof. Dr. Rudack
This innovative methodology allows the team to study transient interactions between RNA and exosome. By tracking the dynamics of individual areas and regions, they are able to get a clearer picture of how these molecular machines go about completing their tasks.
Implications for Future Research
These results from our experiments around exosome composition are giving us new perspectives into the structure and dynamics of the components that comprise an exosome. Their ultimate goal is to further elucidate how these and other movements play key roles in proteins’ functionality.
The researchers are hopeful that these findings will lead to more research opportunities. Specifically, they want to understand how protein movements influence chemical reactions inside a cell.
“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.” – Prof. Dr. Sprangers
The researchers believe that these insights will lay the groundwork for future studies on protein dynamics and their implications for cellular processes.