Context: Proteomics and other high throughput techniques have identified most gene products relevant to cellular processes; the interaction partners of these proteins will be catalogued and most of their structures will be solved. However, a detailed understanding of the structural biophysics of protein-protein interactions is still missing for the great majority of systems. For example, it is not yet possible to accurately dock many proteins in the computer to form a complex or to predict the propensity of structures that undergo conformational changes, e.g. upon membrane binding. These are major challenges, particularly in the case of proteins involved in cell signaling.
Interdisciplinary studies, such as those carried out in my laboratory, provide fundamental insights into how protein dynamics and structural features are used for specific signaling purposes. For example recently, we found an example of a protein-protein complex that is highly dynamic, but utilizes similar interfaces for different protein configurations – only some of which will be compatible with the spatially restricted environment of the proteins near the cellular lipid bilayer. This observation provides insight into the larger question of how signals are transmitted across the cellular membrane