Mass Spectrometry Footprinting Reveals How Kinetic Stabilizers Counteract Transthyretin Dynamics Altered by Pathogenic Mutations_FPOP

Transthyretin (TTR) aggregation causes transthyretin amyloidosis, a severe condition often linked to mutations that destabilize the TTR tetramer, leading to amyloid fibril formation. Small molecules that stabilize the tetramer can prevent this process. While over 300 X-ray structures of TTR exist, they represent static snapshots and fail to show dynamic changes from mutations or ligand binding. This project uses hydrogen-deuterium exchange (HDX) and fast photochemical oxidation of proteins (FPOP) with mass spectrometry (MS) to study these conformational dynamics.