Protein Interactions By Sequence Alone

A general model has been developed for predicting PDZ domain-mediated protein-protein interactions based only on the primary sequence of the domains (Nat. Biotechnol., DOI: 10.1038/nbt.1489). The approach could help researchers decipher the biological functions and potential roles in human disease of PDZ domains, which are a set of protein-binding modules in signaling proteins. Gavin MacBeath of Harvard University and coworkers developed the model by using statistical techniques to analyze the relationship between mouse PDZ sequences and sequences of the peptides they recognize. The method predicts the binding selectivity of the whole PDZ domain family—not only in mice but also in other organisms such as insects and worms. Gary D. Bader of the University of Toronto says methods like the one developed by MacBeath's group will make it possible to predict PDZ-based protein-protein interactions "from the genome," evaluate the functional consequences of PDZ mutations, and engineer useful new PDZ domains.