IDENTIFICATION OF GLUTAMINE AND LYSINE RESIDUES IN ALZHEIMER AMYLOID BETA-A4 PEPTIDE RESPONSIBLE FOR TRANSGLUTAMINASE-CATALYZED HOMOPOLYMERIZATION AND CROSS-LINKING TO ALPHA(2)M RECEPTOR

The beta-amyloid peptide (beta A4), derived from a larger amyloid precursor protein, is the principal component of senile plaques in Alzheimer's disease. Here we report that the full-length (1-40) synthetic beta A4 peptide, containing one glutamine and two lysine residues, is able to form homopolymers in a transglutaminase-mediated reaction. Moreover, transglutaminase catalysed the formation of heteropolymers in reactions of beta A4 with alpha(2)M receptor, a constituent of amyloid plaques, and with extracellular matrix proteins. Incorporation of site-specific probes followed by enzymatic digestion and sequencing of tracer-containing fractions demonstrated that both Lys(16), Lys(28) and Gln(15) in beta A4 were susceptible to cross-linking by transglutaminase.