Evidence for an extended interacting surface between β-amyloid and serum amyloid P component

Studying the interaction between serum amyloid P component (SAP) and β-amyloid (Aβ) a new Aβ binding site was identified on the SAP near the known binding site at the two bound calcium ions. SAP stabilizes deposits in neurodegenerative diseases, which is manifested via Aβ-binding. Because the inhibition of this interaction is a potential therapeutic target in neurodegeneration, the structural basis of SAP-Aβ binding was studied. The chymotryptic digestion of SAP resulted in a 18,223 Da product identified by mass spectrometry. This cleavage was inhibited by Aβ revealing that this cleaving site between Tyr-140 and Gly-141 is involved in the interaction between SAP and Aβ⋅ These results suggest that the Aβ-binding site on SAP is larger than it was recently assumed.