title: Seeing the invisible by paramagnetic and diamagnetic NMR.
abstract: Sparsely populated transient states of proteins and their complexes play an important role in many biological processes including protein-protein and protein-DNA recognition, allostery, conformational selection, induced fit and self-assembly. These states are difficult to study as their low population and transient nature makes them effectively invisible to conventional structural and biophysical techniques. In the present article, I summarize recent NMR developments in our laboratory, including the use of paramagnetic relaxation enhancement, lifetime line broadening and dark-state exchange saturation transfer spectroscopy, that have permitted such sparsely populated states to be detected, characterized and, in some instances, visualized. I illustrate the application of these methods to the elucidation of mechanisms whereby transcription factors locate their specific target sites within an overwhelming sea of non-specific DNA, to the characterization of encounter complexes in protein-protein recognition, to large-scale interdomain motions involved in ligand binding, and to the interaction of monomeric amyloid β-peptide with the surface of amyloid protofibrils and the internal cavity surface of the chaperonin GroEL.
authors.affiliation: *Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, U.S.A.
authors.forename: G Marius
authors.initials: GM
authors.lastname: Clore
mesh_terms: D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins; D004247:DNA