title: Unlocking the secrets to protein-protein interface drug targets using structural mass spectrometry techniques.
abstract: Protein-protein interactions (PPIs) drive all biologic systems at the subcellular and extracellular level. Changes in the specificity and affinity of these interactions can lead to cellular malfunctions and disease. Consequently, the binding interfaces between interacting protein partners are important drug targets for the next generation of therapies that block such interactions. Unfortunately, protein-protein contact points have proven to be very difficult pharmacological targets because they are hidden within complex 3D interfaces. For the vast majority of characterized binary PPIs, the specific amino acid sequence of their close contact regions remains unknown. There has been an important need for an experimental technology that can rapidly reveal the functionally important contact points of native protein complexes in solution. In this review, experimental techniques employing mass spectrometry to explore protein interaction binding sites are discussed. Hydrogen-deuterium exchange, hydroxyl radical footprinting, crosslinking and the newest technology protein painting are compared and contrasted.
authors.forename: Angela
authors.initials: A
authors.lastname: Dailing
authors.affiliation: a Center for Applied Proteomics and Molecular Medicine, Life Sciences Lab Building, George Mason University, 10920 University Boulevard, Manassas, Virginia 20110, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Luchini
authors.affiliation: a Center for Applied Proteomics and Molecular Medicine, Life Sciences Lab Building, George Mason University, 10920 University Boulevard, Manassas, Virginia 20110, USA.
authors.forename: Lance
authors.initials: L
authors.lastname: Liotta
mesh_terms: D000818:Animals; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D058990:Molecular Targeted Therapy / Q000379:methods*; D025941:Protein Interaction Mapping / Q000379:methods*; D020543:Proteome / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
chemical_list: D020543:Proteome
keywords: mass spectrometry; protein complex interface; protein painting; protein–protein interactions; proteomics; targeted therapeutics