Residues in the synuclein consensus motif of the alpha-synuclein fragment, NAC, participate in transglutaminase-catalysed cross-linking to Alzheimer-disease amyloid beta A4 peptide.
The widespread deposition of amyloid plaques is one of the hallmarks of Alzheimer disease (AD). A recently described component of amyloid plaques is the 35-residue peptide, non-A beta component of AD amyloid, which is derived from a larger intracellular neuronal constituent, alpha-synuclein. We demonstrate that transglutaminase catalyses the formation of the covalent non-A beta component of AD amyloid polymers in vitro as well as polymers with beta-amyloid peptide, the major constituent of AD plaques. The transglutaminase-reactive amino acid residues in the non-A beta component of AD amyloid were identified as Gln79 and Lys80. Lys80 is localized in a consensus motif Lys-Thr-Lys-Glu-Gly-Val, which is conserved in the synuclein gene family. Thus transglutaminase might be involved in the formation of insoluble amyloid deposits and participate in the modification of other members of the synuclein family.
Jensen
P H
PH
Department of Medical Biochemistry, University of Aarhus, Denmark.
Sørensen
E S
ES
Petersen
T E
TE
Gliemann
J
J
Rasmussen
L K
LK
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding; D051843:Synucleins; D011503:Transglutaminases / Q000378:metabolism*; D051844:alpha-Synuclein
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D051843:Synucleins; D051844:alpha-Synuclein; D011503:Transglutaminases