Our research group is broadly interested in peptide-binding domains and how only a small number of amino acids are recognized in a given interaction. Specifically, we are focused on the PDZ domain, which is important in signaling and trafficking pathways in the cell. There are over 200 PDZ domains in the human proteome, making it the largest family of peptide-binding domains. Defined motifs include only a couple of positions along the peptide-binding cleft, and do not accurately define the overlapping yet distinct preferences among family members. Our research group will work to understand the selectivity determinants of PDZ domains throughout evolution. We will use biochemistry and structural biology to investigate PDZ domains from extant species, as well as by using ancestral protein reconstruction. We are also interested in the selectivity determinants of other peptide-binding domains, e.g., the SH2 domain, which binds phosphorylated tyrosine-containing peptides.
