Unveiling a Hidden Protein Powerhouse: How FXR Pairs Up for Optimal Functionality
University Park, PA - Prepare to be amazed by the intricate workings of our bodies! A groundbreaking study reveals a hidden talent of a protein that regulates fat, glucose, and cholesterol levels. This protein, known as Farnesoid X receptor (FXR), usually works in harmony with another protein, Retinoid X receptor alpha (RXR). But here's the twist: researchers discovered that FXR can also team up with itself! Penn State scientists have characterized this unique twin pairing, finding that despite its different conformation, it still performs its gene-activating function.
The research, published in Nucleic Acids Research, opens up exciting possibilities for treating liver cancer, diabetes, and other metabolic diseases. By targeting the FXR-FXR complex, therapies could be designed with fewer off-target side effects. The study's lead researcher, Denise Okafor, highlights the potential of this discovery, suggesting that it might reveal a hidden function of FXR that has been overlooked due to its partnership with RXR.
In the lab, the team combined purified FXR with synthetic DNA segments and confirmed that FXR can bind to DNA as a single molecule or in pairs. They further demonstrated that the FXR-FXR pairing could recruit cellular components and drive gene expression. Using small-angle X-ray scattering, the researchers characterized the three-dimensional structure of the FXR-FXR complex, revealing an extended conformation with separated ligand-binding regions, unlike the FXR-RXR pair.
This unique structure suggests that the FXR-FXR pairing may regulate a different set of genes, leading to new insights into its role in metabolic diseases. The study invites further exploration of the genes regulated by this complex and the potential separate roles of the two pairings. Okafor emphasizes the importance of understanding this newly characterized structural variant, as it could unlock new approaches to treating or preventing diseases associated with FXR.
The research team, including Sabab Hasan Khan, Neela Yennawar, and the Penn State Huck Institutes of the Life Sciences, received funding from the U.S. National Institutes of Health, the U.S. National Science Foundation, and the Penn State Huck Institutes. This study showcases how federal support for research drives innovation, making our country safer and more competitive. However, recent funding cuts threaten this progress, emphasizing the need to invest in scientific advancements for a brighter future.
