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Title: Characterisation of the feline leukaemia virus fusion peptide : implications for the fusion mechanism
Author: Davies, S. M. A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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This thesis examines the structure and function of the putative fusion peptide of the retrovirus Feline leukaemia virus, (FeLV), using a variety of mainly biophysical techniques. The structural effects of the FeLV fusion peptide on lipid polymorphism were studied. Using differential scanning calorimetry, 31P nuclear magnetic resonance and time-resolved X-ray diffraction this peptide was found to induce changes in lipid conformation and motion similar to those of known fusogens: it favoured the formation of non-bilayer lipid conformations which have a relatively large negative curvature, namely the inverted hexagonal phase and isotropic lipid states. Moreover, using X-ray diffraction, a new lipid phase was observed in the presence of the FeLV peptide. Neutron diffraction studies revealed a change in the packing of lipid molecules within a bilayer and also possible thinning of the bilayer, both of which were induced by interaction with the FeLV fusion peptide. Fusogenic activity for this putative viral fusion peptide was demonstrated, using fusion assays, which measured the merging of lipid membranes in the presence of the FeLV fusion peptide. These findings are discussed in the light of the current concepts of the fusion mechanism. They add support to two currently favoured theories of fusion: precession by a fusion peptide as a means of inducing the initial destabilisation of a bilayer, and the formation of highly bent, high energy lipid intermediates, such as the 'modified stalk', in the multistep fusion pathway. Circular dichroism was employed to determine the secondary structure of the FeLV fusion peptide under a variety of experimental conditions. This peptide was observed to flip readily between α-helical and β sheet conformations. This suggests that structural plasticity may be an important dynamic property of fusion peptides. Possible relationships between peptide structure and function are discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available