Evidence for an extended interacting surface between beta-amyloid and serum amyloid P component.
Studying the interaction between serum amyloid P component (SAP) and beta-amyloid (Abeta) a new Abeta 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 Abeta-binding. Because the inhibition of this interaction is a potential therapeutic target in neurodegeneration, the structural basis of SAP-Abeta binding was studied. The chymotryptic digestion of SAP resulted in a 18,223Da product identified by mass spectrometry. This cleavage was inhibited by Abeta revealing that this cleaving site between Tyr-140 and Gly-141 is involved in the interaction between SAP and Abeta These results suggest that the Abeta-binding site on SAP is larger than it was recently assumed.
Likó
István
I
Pharmacological & Drug Safety Research, Gedeon Richter Ltd., 1475 Budapest 10, P.O. Box 27, Hungary.
Mák
Marianna
M
Klement
Eva
E
Hunyadi-Gulyás
Eva
E
Pázmány
Tamás
T
Medzihradszky
Katalin F
KF
Urbányi
Zoltán
Z
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000683:Serum Amyloid P-Component; D014443:Tyrosine; D005998:Glycine