Designing Synthetic Receptors for Precise Cell Control
Published:03 Aug.2023 Source:Ecole Polytechnique Fédérale de Lausanne
EPFL professor Patrick Barth and his team developed a novel computational approach for designing protein-peptide ligand binding and applied it to engineer cell-surface chemotactic receptors that reprogrammed cell migration. The researchers created a ‘computational framework’, which is a computer-based system, for designing protein complexes that can change their shape and function dynamically -- as opposed to the conventional static approaches.
The framework can look at previously unexplored protein sequences to come up with new ways for the protein's groups to be activated, even in ways that are different to their natural function. The researchers used their new method to create synthetic receptors that can sense and respond to multiple natural or engineered molecular signals, providing optimal sensing of flexible ligands and strong allosteric signaling responses, a term that refers to changes in protein activity when a molecule binds to a different site on a protein, causing a change in the protein's shape and activity at a different site.
The research shows that combining a flexible sensing layer with a robust signal transmission layer may be a common hallmark of G protein-coupled receptors, a family of enormously important receptors in the cell, connected to virtually every major aspect of its life and function.