Serum amyloid P component

Serum amyloid P component (SAP) is the identical serum form of amyloid P component (AP), a 25kDa pentameric protein first identified as the pentagonal constituent of in vivo pathological deposits called "amyloid" (Cathcart et al, 1967). AP makes up 14% of the dry mass of amyloid deposits (Skinner et al, 1980) and is thought to be an important contributor to the pathogenesis of a related group of diseases called the Amyloidoses (reviewed by Botto et al, 1997). 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. AP is thought to decorate and stabilise aggregates by preventing [[|proteolysis|proteolytic]] cleavage and hence inhibiting fibril removal via the normal protein scavenging mechanisms (Tennent, et al, 1995). 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 (Hawkins & Pepys 1995). 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 (Pepys et al, 2002).

Additional recommended knowledge

How to ensure accurate weighing results every day?

Guide to balance cleaning: 8 simple steps

Safe Weighing Range Ensures Accurate Results

SAP as a pentraxin

SAP is a member of the pentraxins family, characterised by calcium dependent ligand binding and distinctive flattened β-jellyroll structure similar to that of the legume lectins (Emsley J. et al, 1994). The name "pentraxin" is derived from the Greek word for five (penta) and berries (ragos) relating to the radial symmetry of five monomers forming a ring approximately 95Å across and 35Å 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 also found in distant invertebrates such as the horse-shoe crab (Limulus polyphemus) (Pepys et al, 1997).

References

• Botto, M., Hawkins PN, Bickerstaff, M. C., Herbert, J., Bygrave AE, McBride A et al. (1997). Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene. Nat.Med., 3: 855-859.
• Cathcart, E.S., Shirahama, T. and Cohen, A.S. (1967) Isolation and identification of a plasma component of amyloid. Biochim, Biophy. Acta. 147:392
• Emsley, J., White, H.E., O’Hara, B.P., Oliva, G., Srinivasan, N., Tickle, I.J., Blundell, T.L., Pepys, M.B. and Wood S.P. (1994) Structure of pentameric human serum amyloid P component. Nature 367:338-345
• Hawkins P.N. and Pepys M.B. (1995) Imaging amyloidosis with radiolabelled SAP. Eur. J. Nucl. Med. 22:595-599
• Pepys, M. B., Booth, D. R., Hutchinson, W. L., Gallimore, J. R., Collins, P. M., & Hohenester, E. (1997). Amyloid P component. A critical review. Amyloid-International Journal of Experimental and Clinical Investigation, 4: 274-295.
• Pepys, M. B., Herbert, J., Hutchinson, W. L., Tennent, G. A., Lachmann, H. J., Gallimore, J. R., Lovat, L. B., Bartfai, T., Alanine, A., Hertel, C., Hoffmann, T., Jakob-Roetne, R., Norcross, R. D., Kemp, J. A., Yamamura, K., Suzuki, M., Taylor, G. W., Murray, S., Thompson, D., Purvis, A., Kolstoe, S., Wood, S. P., and Hawkins, P. N. (2002) Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature 417(6886), 254-259
• Skinner, M., Pepys, M.B., Cohen, A.S., Heller, L.M. and Lian, J.B. (1980) Amyloid and Amyloidosis. Ed. Glenner, G.G., Pinho e Costa, P. and Falcao de Freitas, F., Excerpta Medica, Amsterdam, 384-391.
• Tennent, G. A., Lovat LB, and Pepys, M. B. (1995). Serum Amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer’s disease and systemic amyloidosis. Proc. Natl. Acad. Sci. U. S. A 92:4299-4303