Seminar

Specificity and promiscuity in protein-ligand interactions

Per Jemth, PhD

Protein-protein and protein-ligand interactions govern most processes in a living organism. However, the vast number of different proteins in any given cell makes it hard to comprehend how they can interact with their physiological binding partner. This question is particularly intriguing because many protein-protein interactions are mediated by a limited number of recognition modules in the form of protein domains. Moreover, each of these recognition modules may have dozens or more putative ligands to choose among. We found that long-range crosstalk between amino acid residues, intradomain allostery, is a possible way to fine-tune specificity in protein-protein interactions. Our hypothesis is that not only the binding pocket but the entire protein domain is optimized to recognize the correct binding partner among all possible ones.