Characterizing the Structure-Function Relationship of Pathological Proteins
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Protein structure and dynamics dictate the fundamentals of protein function. For example, a structured protein must change its conformation when interacting with various ligands. In addition, misfolded or intrinsically disordered proteins (IDPs) oligomerize into more structured aggregates or amyloid fibrils. Therefore, the study of protein conformations becomes necessary to further understand their cellular functions. By monitoring the exchange of backbone amide hydrogens as a measurement of protein dynamics, time-resolved hydrogen-deuterium exchange (TR HDX) provides advantages in capturing the subtle and transient structural differences over other equilibrium state techniques, such as X-ray crystallography and NMR. Using TR HDX together with other biophysical techniques, we demonstrate the unfolding of lipocalin 2 (Lcn2) in accommodating siderophores. In the second part, we attempt to understand the change in aggregation rate corresponding to conformational changes of polyglutamine expansion protein, huntingtin exon1 (Httex1).