GPIDR · Understanding the genetic encoding of dynamic interactions underlying transcriptional regulation

Understanding the genetic encoding of dynamic interactions underlying transcriptional regulation

Protein-protein interactions underlie a wealth of important biological functions. While many of these interactions occur between proteins or parts of proteins that have stable structures, a large portion of them occur in proteins that are interacting in a more dynamic way, often facilitated by so-called "intrinsic disorder". Indeed, one third of the eukaryotic proteome is made up of these intrinsically disordered regions that do not have a stable structure, many of which remain uncharacterized. Understanding how intrinsically disordered proteins engage in dynamic protein-protein interactions not only has important implications for fundamental biology, but also for understanding human disease and enabling drug discovery. In order to address this gap in knowledge, we focused our study on an interaction between a model protein domain (PDZ3) and a disordered peptide (CRIPT). When the domain and peptide interact, one half of the peptide becomes stable, while the other half remains dynamic, or "fuzzy". This feature of the system enabled us to study both modes of interaction in the same system, providing us with directly comparable results that we could use to understand how two aspects of protein binding, affinity (how strongly the protein binds) and specificity (how selectively the protein binds), are encoded for fuzzy and non-fuzzy binding modes.

Data: CORDIS, © European Union