Serum amyloid-P component (SAP) is ubiquitously associated with amyloid deposits and enhance their stability in-vivo. Utilizing a combination of liquid and solid-state NMR techniques we are identifying the motifs present in amyloid fibrils that are recognised by SAP.
Amyloidosis is a family of pathological conditions characterised by the formation of insoluble deposits that lead to the disruption of local tissue. The formation of these deposits has been linked to the mis-folding of normally soluble proteins. Over 20 such proteins have been identified and are linked to a number of socio-economically relevant diseases including Alzheimer’s, Parkinson, Reactive Systemic Amyloidosis and Dialysis Related Amyloidosis. Although each of these diseases are characterised by the mis-folding of a particular protein, common to all deposits is the protein serum amyloid-P component (SAP). In-vivo the binding of SAP to the amyloid deposits is thought to stabilize the insoluble aggregates preventing the host’s defences from clearing them.
The ability of SAP to recognise such a diverse set of amyloid deposits and the absence of any sequence homology between the fibrillar proteins found within them raises the question of the motif that is recognised by SAP. A molecular understanding of this interaction has until recently proved intractable due to the absence of structural data on fibrillar systems. Recent developments in solid-state NMR methodology are now making such studies possible and we are currently using these techniques to understand at a molecular level how SAP interacts with amyloid fibrils composed of beta-2-microglobulin which are typically found in patients suffering from dialysis related amyloidosis.
BBSRC-DTA studentship for Mr Garrick F Taylor
Dr P T F Williamson, Dr J M Werner, Professor S P Wood