Identification of glutamine and lysine residues in Alzheimer amyloid beta A4 peptide responsible for transglutaminase-catalysed homopolymerization and cross-linking to alpha 2M 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 2M 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 Lys16, Lys28 and Gln15 in beta A4 were susceptible to cross-linking by transglutaminase.
Rasmussen
L K
LK
Protein Chemistry Laboratory, University of Aarhus, Denmark.
Sørensen
E S
ES
Petersen
T E
TE
Gliemann
J
J
Jensen
P H
PH
D000544:Alzheimer Disease; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005973:Glutamine / Q000032:analysis*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008239:Lysine / Q000032:analysis*; D008969:Molecular Sequence Data; D011108:Polymers / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D011503:Transglutaminases / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D003432:Cross-Linking Reagents; D016326:Extracellular Matrix Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011108:Polymers; D011971:Receptors, Immunologic; D005973:Glutamine; D011503:Transglutaminases; D008239:Lysine