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Eaton, William Allen
Anno di nomina: 2011
Email: eaton [@] nih.gov.
NIH Distinguished Investigator, Chimico biofisico, Direttore del Laboratorio di Chimica Fisica nel National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health di Bethesda, MD (U.S.A.).
Protein aggregation: Eaton discovered the highly unusual kinetics of hemoglobin S aggregation, characterized by a delay period inversely proportional to the ~30th power of the protein concentration and explained these kinetics with a novel double nucleation mechanism. Eaton recognized that the unusual kinetics of hemoglobin S aggregation play a central role in the pathophysiology of sickle-cell disease. He proposed that even a small reduction in intracellular hemoglobin S concentration would have a significant therapeutic effect by increasing the delay time, allowing more red cells to escape the microcirculation before the onset of polymerization. The only successful specific drug for sickle cell disease (hydroxyurea) works by this precise mechanism.
Protein allostery: From oxygen binding measurements on single crystals of hemoglobin in polarized light, Eaton and coworkers at the University of Parma effectively settled a 25-year controversy by unambiguously demonstrating that cooperative oxygen binding requires a change in quaternary structure, as postulated in the famous allosteric model of Monod, Wyman, and Changeux (MWC).
Protein folding: Eaton pioneered the application of a range of physical methods using nanosecond pulsed lasers to dramatically improve the time resolution in studies of folding kinetics. His concept of a “speed limit” for protein folding motivated the search for ultrafast-folding proteins, allowing direct comparisons of experiments with atomistic molecular dynamics simulations. Eaton also pioneered single-molecule fluorescence methods to address fundamental issues in protein folding dynamics, including the first determination of the transition path (barrier crossing) time, not previously measured for any molecular system.