Structural Insights into the CRTC2-CREB Complex Assembly on CRE Revealed by Prague Researchers

Posted on May 20, 2023 • 3 minutes • 459 words

New research conducted in Prague has shed light on the structural insights into the CRTC2-CREB complex assembly on CRE. The study, published today in the prestigious scientific journal Nature, reveals crucial information about the interactions between these proteins and how they work to regulate gene expression.

The CRTC2 and CREB proteins play an important role in the signaling pathways of cells, particularly in response to external stimuli such as stress or nutrient availability. When activated, they form a complex that binds to specific DNA sequences known as CREs, which are found near genes that need to be turned on or off.

Using a combination of X-ray crystallography and molecular dynamics simulations, the team of researchers at the Institute of Biophysics, Academy of Sciences of the Czech Republic, was able to capture detailed images of the CRTC2-CREB complex as it binds to CREs. They found that the interaction involves a highly specific network of hydrogen bonds and electrostatic interactions, which ensure that the proteins bind tightly to their target.

“This study provides the most accurate picture yet of how the CRTC2-CREB complex assembles on CREs to regulate gene expression,” said Dr. Jan Dohnalek, one of the lead authors of the study. “The insights we gained could have important implications for understanding diseases such as cancer and diabetes, which are characterized by dysfunctional gene expression mechanisms.”

The researchers also discovered that the CRTC2-CREB complex undergoes a structural change upon binding to CREs, which exposes a previously hidden surface that is required for its activity. This finding has significant implications for drug development, as it may be possible to design molecules that target this specific area to modulate gene expression in a more selective manner.

The study represents a significant advance in the field of protein-protein interactions and provides new tools for understanding the molecular mechanisms that underlie the regulation of gene expression. It is part of a larger effort to unravel the complex network of signaling pathways that controls cell behavior and how it is disrupted in diseases.

“Our hope is that these findings will inspire further studies that investigate the regulation of gene expression in more detail,” said Dr. Dohnalek. “We believe that a better understanding of this process will be essential for the development of new therapies that target the underlying molecular mechanisms of disease.”

Overall, this research represents a major contribution to the field of molecular biology and has the potential to impact many areas of medicine. The insights gained from this study could lead to new treatments for diseases that have thus far proven resistant to conventional therapies. As the team at the Institute of Biophysics continues its groundbreaking work, we can expect even more exciting discoveries to emerge from this research in the years to come.