Coker, Rebecca;
(2018)
The Role of Serum Amyloid P in Amyloidosis.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Amyloid is a term used to describe a set of diseases caused by protein misfolding. There are 36 proteins known to undergo amyloidosis to date. They each unfold from their unique native states and refold into a specific cross β- sheet motif to which various macromolecules can bind. These protein deposits invade tissues and organs disrupting tissue structure and function. The protein serum amyloid P (SAP) is a universal component to all amyloid deposits regardless of the protein involved. It is a disc shaped protein which is known to protect amyloid fibres against degradation. The role of SAP in amyloidosis has been a subject of discussion for many years. Some have found SAP to enhance fibre formation whereas others have found SAP to prevent it. This thesis can be divided into two parts. The first half focuses on the molecular analysis of SAP in relation to amyloid fibre growth whereas the second half focuses solely on the structural aspects of SAP. Chapters 2 and 3 demonstrate that SAP actually exhibits a dual role in relation to fibrillogenesis. It is capable of acting as both a chaperone and a fibrillogenic enhancer depending on its conformation at the time. As a monomer SAP is responsible for the enhancement and stabilisation of fibres whereas in its dimerised form it demonstrates characteristics similar to that of a molecular chaperone. Recent developments in amyloid treatment involve the removal of SAP from deposits using anti-SAP antibodies. As of yet, structural analysis has not been carried out on the SAP:antibody complex. Chapters 4 and 5 conclude this thesis by using crystallographic techniques to demonstrate that a single antibody binds to an SAP molecule during dissociation from amyloid deposits.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The Role of Serum Amyloid P in Amyloidosis |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10055802 |
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