Understanding unstable proteins

Multifunctional protein

The study focused on a folded segment known as the cold-shock domain (CSD/CSDex) within the YB1 protein, an IDP with multiple functions in the cell. The researchers wanted to know how this segment maintains its structural stability. The protein is involved in many of the cell’s most important activities, including the reading of genes, production of proteins, and processing of RNA. “Because of its close link to cancer growth and drug resistance, understanding how the YB1 protein folds and functions could help in developing new treatment methods,” hopes doctoral student Shrestha.

The team found that the CSDex protein exhibits moderate stability under physiological conditions. Half of the molecule is in its folded structure while the other half remains unfolded. If the protein binds to nucleic acids, it entirely transitions into its folded state. “This indicates that these interactions stabilize the protein in a way that helps fix it in its functional form,” says Ebbinghaus.

Knowledge for treating diseases

The team also shows that the protein can take on many different structures, thereby facilitating quick and efficient interaction with a range of nucleic acids. The moderate stability of CSDex could present a natural compromise that gives it the flexibility to efficiently interact with many different molecules while performing numerous functions.

“CSDex-nucleic acid interactions result in an overproduction of different proteins or the repair of nucleic acids, for example, which makes cancer cells more resistant to chemotherapy,” explains Shrestha. Future research could develop molecules that target CSDex-nucleic complexes and specifically block disease-related interactions.