Levels of supramolecular chirality of polyglutamine aggregates revealed by vibrational circular dichroism

• PolyQ fibril aggregates exhibit enhanced VCD and supramolecular chiral organization that differ from all previously observed amyloid fibrils.
• Q ⩾ 35 aggregates show a further enhanced level of supramolecular chiral organization compared to Q ⩽ 30 aggregates.
• Q ⩾ 35 and Q ⩽ 30 fibril aggregates exhibit the same secondary structure and VCD intensity pattern..

Polyglutamine (PolyQ) aggregates are a hallmark of several severe neurodegenerative diseases, expanded CAG-repeat diseases in which inheritance of an expanded polyQ sequence above a pathological threshold is associated with a high risk of disease. Application of vibrational circular dichroism (VCD) reveals that these PolyQ fibril aggregates exhibit a chiral supramolecular organization that is distinct from the supramolecular organization of previously observed amyloid fibrils. PolyQ fibrils grown from monomers with Q repeats 35 and above (Q ⩾ 35) exhibit approximately 10-fold enhancement of the same VCD spectrum compared to the already enhanced VCD of fibrils formed from Q repeats 30 and below (Q ⩽ 30).