Molecular Imaging of Protein–Protein Interactions and Protein Folding

In the last 2 decades, there has been significant interest in the field of reporter gene imaging, with the aim of determining the location(s), duration, and extent of gene expression within living subjects. An important application of this is in molecular imaging of interacting protein partners and protein conformational changes, an area that could pave the way to functional proteomics in living animals and provide a tool for whole-body evaluation of new pharmaceuticals targeted to modulate protein–protein interactions and protein misfolding. We review the three general methods currently available for imaging protein–protein interactions in living subjects using reporter genes, namely a modified mammalian two-hybrid system, a bioluminescence resonance energy transfer system, and split reporter protein complementation and reconstitution strategies.