Scientists have known for years that chemokines and G protein-coupled receptors (GPCRs) guide how cells move, but the complexity of their interactions remained elusive. Now, researchers from St. Jude Children's Research Hospital and the Medical College of Wisconsin have uncovered how these proteins selectively bind to control cellular movement.

In their published study, the team developed a data science framework that analyzes protein structure and sequence data at a deep level. Their approach revealed that both structured and disordered regions of chemokines and GPCRs work together to determine which proteins bind,  directing the movement of cells.

Dr. M. Madan Babu of St. Jude Children's Research Hospital and co-corresponding author, said:

"We found that cells have an elegant system that uses structure and disorder together to control cell migration. With that understanding, we can now rationally introduce small changes in a chemokine's structure to ultimately alter cell migration in desired ways."

The scientists discovered that small, disordered regions of these proteins function much like private encryption keys, while the structured regions act as public keys. When working in tandem, they form a unique identifier that ensures cells respond only to specific chemokine-GPCR pairs. This system governs migration with precision, just like secure transactions online.

With this insight, the researchers succeeded in manipulating protein regions to change their binding preferences. They tweaked a chemokine's structure and changed how T cells responded, altering how these cells move.

St. Jude's Dr. Andrew Kleist, the study's first and co-corresponding author, said:

"Now that we've shown a proof of concept, our approach will guide exploration into new medicines and improvements for existing cellular therapies. For example, it may be possible to create molecules that better lead immune cells to cancers or help recruit more blood stem cells for bone marrow transplants. In theory, any therapy using cell movement could benefit from applying these principles."

Read the full article here to learn more about the science behind chemokines and GPCRs. 

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