Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.602980
Title: Complementary studies of the role of metals in the conformation and interactions of serum amyloid P component and β-amyloid Aβ42
Author: Mold, Matthew John
Awarding Body: Keele University
Current Institution: Keele University
Date of Award: 2013
Availability of Full Text:
Full text unavailable from EThOS. Restricted access.
Please contact the current institution’s library for further details.
Abstract:
Serum amyloid P component (SAP) is a conserved member of a family of cyclic oligomeric calcium-binding proteins and has been found in species as diverse as humans and the horseshoe crab, Limulus polyphemus. The presence of the serum pentraxins have been deemed essential within invertebrates due to their lack of an adaptive immunity, in contrast with the adaptive immunoglobulin-based antibody immunity displayed in humans in which the pentraxins have been shown to play a pivotal role in the recognition and destruction of disease causing pathogens. In spite of the potential role of SAP within the human immune response, SAP is also known to bind, stabilise and promote the formation of amyloid fibrils in vitro, which are the abnormal protein aggregates responsible for the amyloidosis diseases. Amyloid fibrils have no known functional properties, yet their extracellular deposition in the spaces of numerous tissues has been associated with neurodegenerative diseases, including pamyloid (specifically AP42), in Alzheimer's disease (AD). Transmission electron microscopy analyses performed herein demonstrated that SAP accelerated the formation and enhanced the stability of amyloid fibrils in a physiologically significant undersaturated solution of Ap42. Glycosaminoglycans are also found associated within amyloid plaques in AD and herein crystallographic analyses supported their calcium-dependent binding to Limulus SAP. Human SAP has been shown to bind to polysaccharide and proteinaceous ligands both calcium-dependently and independently. X-ray crystallographic analyses have for the first time identified a potential Cu(II) binding site away from the known calcium-binding site of the protein. The results show that the residues His I 0 I and Cys37 appear to be critical for the coordination of the divalent metal ion to the protein. Overall these results support the recent attempts to target human SAP as a possible therapy for AD.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.602980  DOI: Not available
Share: