Breaking the coupling process

October 06, 2020

Proteins transduce information and signals within the human body by changes in their structures. For example, hormones binding to their target proteins cause a structural change which in turn opens new binding sites for other proteins elsewhere on the surface of the protein. Researchers refer to this coupling of different, distant binding sites as allostery. An interruption of this coupling leads to signals not being passed on.

This can be achieved by molecules specifically designed for this purpose, which thereby obtain pharmacological effects as analgesics or chemotherapeutic agents. To selectively design such molecules, scientists need to learn more about the possible mechanisms of allostery. A team led by Prof. Dr. Gerhard Stock from the Biomolecular Dynamics group at the Institute of Physics at the University of Freiburg and Prof. Dr. Peter Hamm from the Institute of Chemistry at the University of Zurich, Switzerland provides important insights into the molecular details of allostery in the journal PNAS.

The researchers tracked time-resolved allosteric changes in the test protein PDZ2, which are caused by the binding of a peptide ligand. To this end, the research group at the University of Zurich performed time-resolved vibrational spectroscopy, while the physicists at the University of Freiburg simulated the corresponding changes on an atomistic level using the bwHPC cluster BinAC at Tübingen. This combination enabled the scientists to understand how a change in the ligand binding mode induces protein structure changes passing through the protein with atomic resolution and a time scale range from picoseconds to microseconds. The real-time observation of signal transduction in proteins showed that allostery is based on changes in both the structure and dynamics of the protein, which exhibits hierarchical dynamics, where a structural change takes about ten times longer than a preceding change.
Original publication: Bozovic, O., Zanobini, C., Gulzar, A., Jankovic, B., Buhrke, D., Post, M., Wolf, S., Stock, G., Hamm, P. (2020): Real-time observation of ligand-induced allosteric transitions in a PDZ domain. In: PNAS. DOI: 10.1073/pnas.2012999117


Institute of Physics
Faculty for Mathematics and Physics
University of Freiburg

University of Freiburg

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to