Per Jemth: "The energetic landscape of protein-protein interactions"

The energetic landscape of protein-protein interactions

Protein-protein interactions govern cell signalling and scaffolding. There are a few very common protein-protein interaction domains in the cell, modular entities with distinct specificities towards various ligands. One of the most widespread of these interaction modules is the PDZ domain with a few hundred members in humans. PDZ domains bind a large variety of proteins, often at their C-terminus to facilitate, for example phosphorylation or cellular localization. The C-terminus of the ligand protein is often disordered, that is, it does not adopt a well-defined conformation in the unbound state. Upon binding, the C-terminus becomes ordered as part of a beta-sheet in the PDZ domain. By using protein engineering in conjunction with kinetic experiments we have obtained a detailed picture of how this disordered ligand binds to the PDZ domain. Basic principles and general conclusions about this protein-ligand interaction will be discussed.