The study of protein fold is a central problem in life science, leading in the
last years to several attempts for improving our knowledge of the protein
structures. In this thesis this challenging problem is tackled by means of
molecular dynamics, chirality and NMR studies.
In the last decades, many algorithms were designed for the protein secondary
structure assignment, which reveals the local protein shape adopted by segments of amino acids. In this regard, the use of local chirality for the protein
secondary structure assignment was demonstreted, trying to correlate as well
the propensity of a given amino acid for a particular secondary structure.
The protein fold can be studied also by Nuclear Magnetic Resonance (NMR)
investigations, finding the average structure adopted from a protein. In this
context, the effect of Residual Dipolar Couplings (RDCs) in the structure refinement was shown, revealing a strong improvement of structure resolution.
A wide extent of this thesis is devoted to the study of avian prion protein.
Prion protein is the main responsible of a vast class of neurodegenerative
diseases, known as Bovine Spongiform Encephalopathy (BSE), present in
mammals, but not in avian species and it is caused from the conversion of
cellular prion protein to the pathogenic misfolded isoform, accumulating in
the brain in form of amiloyd plaques. In particular, the N-terminal region,
namely the initial part of the protein, is quite different between mammal
and avian species but both of them contain multimeric sequences called Repeats, octameric in mammals and hexameric in avians. However, such repeat
regions show differences in the contained amino acids, in particular only
avian hexarepeats contain tyrosine residues. The chirality analysis of avian
prion protein configurations obtained from molecular dynamics reveals a high
stiffness of the avian protein, which tends to preserve its regular secondary
structure. This is due to the presence of prolines, histidines and especially tyrosines, which form a hydrogen bond network in the hexarepeat region, only
possible in the avian protein, and thus probably hampering the aggregation.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:1051 |
| Date | 16 April 2008 |
| Creators | Pietropaolo, Adriana <1981> |
| Contributors | Zannoni, Claudio |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | English |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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