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Title: The structure and physical properties of amyloid fibrils
Author: Fitzpatrick, Anthony William Paul
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2009
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Amyloid fibrils are associated with a range of highly debilitating neurological disorders including Alzheimer’s disease, Parkinson’s disease and the spongiform encephalopathies. These structures are formed by the misfolding and self-assembly of peptides and proteins varying widely in sequence and in native conformation. Here we combine experimental measurements derived from sold-state NMR, X-ray fibre diffraction and Atomic Force Microscopy to determine the complex, higher order protofilament structure adopted by an 11-amino acid peptide fragment of the human plasma protein transthyretin, TTR(105-115). This determination of the structure of amyloid fibrils to atomic resolution is crucial to the understanding of non-native protein self-assembly and the molecular basis of protein deposition diseases. We then demonstrate that amyloid fibrils, ordered supramolecular structures that we self-assemble from a wide range of polypeptide molecules, constitute a class of high-performance biomaterials and that rigidity of the fibrils can be tuned over four orders of magnitude. We elucidate the molecular origin of their material properties, and show that the major contribution to fibril rigidity stems from a generic inter-backbone hydrogen bonding network that is modulated by variable side-chain interactions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available