Mass spectrometry based footprinting of membrane proteins
Resolving the difficulties with unstable membrane proteins, such as human VKOR, inspired us to develop methods of probing membrane protein structure in live cells. Our first key insight was that mass spectrometry-based footprinting is not subject to the limitation that membrane proteins are often unstable in detergents, a problem severely hindering conventional structural biology with purified proteins. We generate protein footprints in live cells, and the detergent stability of this protein is no longer a concern. Second, we have shown that footprinting can probe the dynamic motions and interactions of membrane proteins during various cellular processes, which are often beyond the reach of traditional methods. This method is broadly applicable to the study of membrane proteins.
