By Jane Smith | BOSTON – 2025/06/22 12:15:38

scientists have gained new insights into how cells maintain order at the molecular level, which could lead to innovative approaches for preventing cancer progression. The research focuses on the interaction between two key proteins,paxillin and focal adhesion kinase (FAK),within cellular structures called focal adhesions.

In 1995, a researcher and his colleagues at Harvard were the first to clone the full-length human gene.

To understand paxillin’s function, the team investigated its relationship with FAK. This examination proved challenging because the two proteins share numerous binding residues and are constantly changing.Paxillin is also a highly disordered protein.

The team narrowed its focus to the most important structures. They discovered that when paxillin and the C-terminal targeting domain of FAK (FAT) interact at a specific docking site, they must shrink and remain compact to fit within a confined space. However, they maintain considerable flexibility when interacting with the broader focal adhesion network.

Novel Protein Interaction Mechanism

“our results point to a novel mechanism of protein interaction that is less studied in the literature and indicates the possibility of such mechanisms to be applicable to othre disordered proteins,” said Dr. Salgia. “This study has broad implications for disordered proteins in general.”

“Our results point to a novel mechanism of protein interaction that is less studied in the literature.”

According to the researchers, such protein interactions are typically difficult to target with drugs as there is no clear binding site. However, by capturing the interaction, Dr. Salgia and his team developed a model that could help other researchers identify a moving target.

Advanced Techniques Enable Discovery

The discovery was made possible through sophisticated laboratory techniques. The team used a type of spectroscopy related to medical magnetic resonance imaging (MRI), often used in physics, to better understand paxillin’s structural characteristics.They then combined spectroscopy with dynamic simulations to show how paxillin binds to FAT. they created a 3D computer model to illustrate the interaction.

“The combination of all these methods enabled us to accurately characterize the structural features of the paxillin-FAK interaction more than any single method on its own,” said Supriyo Bhattacharya, Ph.D., assistant research professor in the Department of Computational and Quantitative Medicine at City of Hope, the first and co-senior author and lead in protein structure and data analysis in the study.

In addition to Dr. Salgia and City of Hope authors Bhattacharya and Prakash kulkarni, ph.D., a research professor in the Department of Medical Oncology & Therapeutics Research at City of Hope (an expert in disordered protein), the team included researchers from the University of Maryland, John Orban, Ph.D., (co-senior author and expert in spectroscopic techniques), and the National Institute of Standards and Technology.