12 November 2021
Kimberly Reynolds
Green Center for Systems Biology
UT Southwestern Medical Center
Long-range interactions between amino acids play a key role in several aspects of protein function. Nowhere is this more obvious than in allosteric regulation, in which a signal at one protein surface modulates activity at another spatially distinct site. Allostery is a common feature of natural proteins, and an ability to engineer new allostery would be of immense practical value for the design of custom biosensors, research reagents, and allosterically acting pharmaceuticals. So how might allostery evolve in natural proteins? By answering this question, we hope to distill principles for creating engineered proteins that function like their natural counterparts. My group uses a combination of co-evolutionary analysis, synthetic fusions between input and output protein domains, and high-throughput saturation mutagenesis. I will present our results showing how a spatially distributed set of surface positions can contribute to tuning and optimizing allosteric regulation in a newly established synthetic allosteric switch.