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Oral Sessions
Day 3, June 24（Tue.） 11:40-11:55
Room C (Top of Yaima)
- 3C-O1-1140
Xlinking MS for structure analysis of tau/phosphorylated tau and other proteins
(PTB)
oCristian Arsene, Anne-Katrin Römmert
The higher-order structure of proteins is critical to their biological function, with structural alterations potentially leading to dysfunctional physicochemical properties. Understanding these changes is especially important for biomarker proteins associated with neurodegenerative diseases like Alzheimer's disease, as they influence protein aggregation and the formation of cytotoxic intracellular neurofibrillary tangles. This presentation examines a study focused on identifying differences in the higher-order structure of proteins, particularly phosphorylated and non-phosphorylated recombinant Tau protein in solution.
Crosslinking mass spectrometry (XL-MS) was utilized for structural analysis, providing essential information about distance constraints and protein structures in solution. Bovine serum albumin (BSA) was used as a model, with conditions adjusted to induce structural changes. Covalently bound cross-linkers "froze" these structures, and bottom-up proteomics was employed to analyze the cross-linked peptides. Topological (structural) differences and similarities were explored through network maps including both the linkages between XL amino acid positions and the original protein sequence. Element-centric similarity scores were calculated from pair-wise clustering data.
This methodology was applied to Tau proteins to investigate folding states over time during in-vitro aggregation. Preliminary results reveal significant structural differences, offering insights into protein aggregation mechanisms.