Abstract
Engineering processes and proteins to control aggregation behavior has been hindered by the lack of detailed information about the mechanisms of protein aggregation. In the studies described here, hydrogen-deuterium isotope exchange detected by mass spectrometry (HX-MS) has revealed kinetic, thermodynamic, and structural aspects of model and pharmaceutical protein unfolding under destabilizing, aggregation conditions. First, hen egg white lysozyme was studied during salt-induced precipitation. Bimodal mass distributions in the HX-MS-labeling experiments for precipitates indicated that lysozyme continues to exhibit two-state unfolding behavior under these conditions, with the denatured state being only partially unfolded, resembling molten globule states observed in other folding studies.
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Fernandez, E.J., Tobler, S.A. (2006). Elucidating Structure, Stability, and Conformational Distributions during Protein Aggregation with Hydrogen Exchange and Mass Spectrometry. In: Misbehaving Proteins. Springer, New York, NY. https://doi.org/10.1007/978-0-387-36063-8_4
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DOI: https://doi.org/10.1007/978-0-387-36063-8_4
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