Physical Sciences and Mathematics Commons^™

Structural Characterization Of The Pre-Amyloid Oligomers Of Β-2-Microglobulin Using Covalent Labeling And Mass Spectrometry, Vanessa Leah Castillo Mendoza

Open Access Dissertations

The initial steps involved in the assembly of normally soluble proteins into amyloid fibrils remain unclear, yet over 20 human diseases are associated with proteins that aggregate in this manner. Protein surface modification is a potential means of mapping the interaction sites in early oligomers that precede amyloid formation. This dissertation focuses on the use of covalent labeling combined with mass spectrometry to elucidate the structural features of Cu(II)-induced β-2-microglobulin (β2m) amyloid formation. An improved covalent modification and MS-based approach for protein surface mapping has been developed to address the need for a reliable approach that ensures protein structural integrity …