Identifying differences in dynamics and residual structure of the intrinsically disordered domains of α-synuclein monomer and fibers

Abstract

Amyloid fibrils (AFs) are a hallmark of several incurable neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. AFs are insoluble protein aggregates with a cross-β fibril core that often comprise highly flexible domains in the N or C-termini. Many AFs, including α-synuclein (α-syn) and amyloid-β, form polymorphs. Polymorphism, in this context, enables a protein to fold and self-propagate into different AF structures often accompanied by varying neuropathology. α-Syn is natively found as a soluble intrinsically disordered protein, but in Parkinson’s disease it misfolds and aggregates into AFs found in Lewy bodies.