| Abstract
Protein-protein interactions mediate essentially all biological processes.
A detailed understanding of these interactions is thus a major goal
of modern biological chemistry. Three dimensional structures, obtained
with either NMR and X-ray crystallography methods, have provided considerable
insights into the mechanisms of proteins binding. However, these methods
are low throughput, labour intensive, and require large amount of high
purity sample. Mass spectrometry is emerging as a powerful alternative
technique to study protein-protein interaction, protein folding and
conformation with the aim to determine 3D structure by coupling with
protein structure modeling computation.
Mass spectrometry has been applied to study both gas and solution phase
protein structures. Electron capture dissociation is an efficient protein
backbone dissociation method without disrupting its tertiary structure.
If protein fragments are held together by intramolecular non-covalent
bond, then the product detected is (M+nH)(n-1)+. The application of
this method to study gas phase protein ion conformation and folding
will be discussed.
For protein structure in solution, protein footprinting maps the solvent
accessible protein surface by chemical modification in solution coupled
with mass spectrometry detection of modified surface residues. It can
also be used to examine protein-protein interaction in solution. We
have developed a pulse method to produce extensive protein surface modification.
Both top down and bottom up mass spectrometry approaches of protein
analysis have been applied to map the modified amino acids on protein
surface.
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