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 prec ursor protein, is the principal component of senile plaques in Alzheim er's disease. Here we report that the full-length (1-40) synthetic bet a A4 peptide, containing one glutamine and two lysine residues, is abl e to form homopolymers in a transglutaminase-mediated reaction. Moreov er, transglutaminase catalysed the formation of heteropolymers in reac tions of beta A4 with alpha(2)M receptor, a constituent of amyloid pla ques, and with extracellular matrix proteins. Incorporation of site-sp ecific 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.