Origin of enhanced VCD in amyloid fibril spectra: Effect of deuteriation and pH

• Published in: Chirality (New York, N.Y.) N.Y.), 2017-09, Vol.29 (9), p.469-475
• Main Authors: Pazderková, Markéta, Pazderka, Tomáš, Shanmugasundaram, Maruda, Dukor, Rina K., Lednev, Igor K., Nafie, Laurence A.
• Format: Article
• Language: English
• Subjects: Amyloid; Amyloid - chemistry; Animals; Atomic force microscopy; Chirality; Circular Dichroism; Deuterium; Deuterium - chemistry; deuterium exchange; Dichroism; Fibrils; Humans; Hydrogen-Ion Concentration; Insulin; Insulin - chemistry; Lysozyme; Molecular structure; Morphology; Muramidase - chemistry; Neurodegenerative diseases; pH effects; Polymorphism; Protein Aggregates; protein fibrils; Proteins; Spectra; supramolecular chirality; VCD intensity enhancement origin; vibrational circular dichroism
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.22722

Supramolecular chirality of amyloid fibrils, protein aggregates related to many neurodegenerative diseases, is a remarkable property associated with fibril structure and polymorphism. Since its discovery almost 10 years ago there is still little understanding of this phenomenon, including the cause of the highly enhanced vibrational circular dichroism (VCD) intensity arising from fibril supramolecular chirality. In this study, VCD spectra, enhanced by filament supramolecular chirality, are presented for lysozyme and insulin fibrils above and below pH 2 and after deuterium exchange, above and below pD 2. Supramolecular chirality (observed by VCD) and fibril morphology (documented by atomic force microscopy) are not affected by protein deuteriation. In D2O the fibril VCD sign pattern changes to fewer bands, with implications for the amide I/II origin of enhanced VCD intensity. Separation of amide I and II signals will facilitate calculations of enhanced VCD spectra of amyloid fibrils and enable a better understanding of the origin of the VCD sign pattern. Enhanced VCD for lysozyme in H2O in the overlapped amide I/II region with sign pattern (++ − ++) simplifies to separated amide I′ and amide II’ in D2O with sign pattern (++ − +) with negligible VCD enhancement from the amide II’ band. Decoupling the amide II vibration by deuteriation provides a new and simpler sign pattern for future computational studies aiming to understand the origin of enhanced supramolecular chirality in amyloid fibrils.