Ensembles of interconverting protein complexes with multiple interaction domains

Many critical biological processes depend on protein complexes that exist as ensembles of subcomplexes rather than a discrete complex. The subcomplexes dynamically interconvert with one another, and the ability to accurately resolve the composition of the diverse molecular species in the ensemble is crucial for understanding the contribution of each subcomplex to the overall function of the protein complex. Advances in computational programs have made it possible to predict the various molecular species in these ensembles, but experimental approaches to identify the pool of subcomplexes and associated stoichiometries are often challenging. This review highlights some experimental approaches that can be used to resolve the diverse molecular species in protein complexes that exist as ensembles of sub complexes.