Tau protein from Alzheimer's disease patients is glycated at its tubulin-binding domain.
Glycated residues of tau protein from paired helical filaments isolated from the brains of Alzheimer's disease patients were localized by doing a proteolytic cleavage of the protein, fractionation of the resulting peptides, and identification of those peptides using specific antibodies. The most suitable residues for glycation, lysines, present at the tubulin-binding motif of tau protein, seem to be preferentially modified compared with those lysines present at other regions. Among these modified lysines, those located in the sequence comprising residues 318-336 (in the largest human tau isoform) were found to be glycated, as determined by the reaction with an antibody that recognizes a glycated peptide containing this sequence. Because those lysines are present in a tubulin binding motif of tau protein, its modification could result in a decrease in the interaction of tau with tubulin.
Ledesma
M D
MD
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
Bonay
P
P
Avila
J
J
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D006031:Glycosylation; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D010446:Peptide Fragments; D014404:Tubulin; D016875:tau Proteins; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase