Serum amyloid P component

In amyloidosis

SAP makes up 14% of the dry mass of amyloid deposits and is thought to be an important contributor to the pathogenesis of a related group of diseases called the Amyloidoses. These conditions are characterised by the ordered aggregation of normal globular proteins and peptides into insoluble fibres, which disrupt tissue architecture and are associated with cell death. Contributing to its role in pattern recognition immune clearance, SAP binds in a calcium dependent manner to complement component C1q and the antibody binding region of immunoglobulins (Fab). SAP is thought to decorate and stabilise aggregates by preventing proteolytic cleavage and hence inhibiting fibril removal via the normal protein scavenging mechanisms. This association is utilised in the routine clinical diagnostic technique of SAP scintigraphy whereby radio-labelled protein is injected into patients to locate areas of amyloid deposition. The SAP-amyloid association has also been identified as a possible drug target for anti-amyloid therapy, with the recent development and first stage clinical trials of a compound called CPHPC (R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxohexanoyl] pyrrolidine-2-carboxylic acid), a small molecule able to strip AP from deposits by reducing levels of circulating SAP.

Structure

SAP is a member of the pentraxins family, characterised by calcium-dependent ligand binding and a distinctive flattened β-jellyroll structure similar to that of the legume lectins. The name "pentraxin" is derived from the Greek words for five (penta) and berries (ragos), relating to the radial symmetry of five monomers forming a ring approximately 95 across and 35 deep. Human SAP has 51% sequence homology with C-reactive protein (CRP), a classical acute phase response plasma protein, and is a more distant relative to the "long" pentraxins such as PTX3 (a cytokine-modulated molecule) and several neuronal pentraxins. Both SAP and CRP are evolutionary conserved in all vertebrates and are also found in distant invertebrates such as the horseshoe crab (Limulus polyphemus).

References

References

1. (1967). "Isolation and identification of a plasma component of amyloid". Biochim. Biophys. Acta.
2. "Entrez Gene: APCS amyloid P component, serum".
3. (1980). "Amyloid and amyloidosis: proceedings of the Third International Symposium on Amyloidosis, Póvoa de Varzim, Portugal, 23–28 September 1979". Excerpta Medica.
4. (August 1997). "Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene". Nature Medicine.
5. Bristow CL, Boackle RJ. Evidence for the binding of human serum amyloid P component to Clq and Fab gamma. Mol Immunol. 1986 Oct;23(10):1045-52. doi: 10.1016/0161-5890(86)90003-9. PMID: 3099175.
6. (May 1995). "Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis". Proceedings of the National Academy of Sciences of the United States of America.
7. (July 1995). "Imaging amyloidosis with radiolabelled SAP". European Journal of Nuclear Medicine.
8. (May 2002). "Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis". Nature.
9. (January 1994). "Structure of pentameric human serum amyloid P component". Nature.
10. (1997). "Amyloid P component. A critical review". Amyloid.