O-GlcNAcylation modulates the self-aggregation ability of the fourth microtubule-binding repeat of tau.
In Alzheimer's disease (AD), tau protein is abnormally hyperphosphorylated and aggregated into paired helical filaments (PHFs). It was discovered recently that tau is also O-GlcNAcylated in human brains. And O-GlcNAcylation may regulate phosphorylation of tau in a site-specific manner. In this work, we focused on the fourth microtubule-binding repeat (R4) of tau, which has an O-GlcNAcylation site-Ser356. The aggregation behavior of this repeat and its O-GlcNAcylated form was investigated by turbidity, precipitation assay and electron microscopy. In addition, conformations of these two peptides were analyzed with circular dichroism (CD). Our results revealed that O-GlcNAcylation at Ser356 could greatly slow down the aggregation speed of R4 peptide. This modulation of O-GlcNAcylation on tau aggregation implies a new perspective of tau pathology.
Yu
Chun-Hui
CH
Department of Chemistry, Beihua University, Jilin 132013, PR China.
Si
Tong
T
Wu
Wei-Hui
WH
Hu
Jia
J
Du
Jin-Tang
JT
Zhao
Yu-Fen
YF
Li
Yan-Mei
YM
D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism*; D000215:Acylation; D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D020449:Repetitive Sequences, Amino Acid; D012694:Serine / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
C054369:MAPT protein, human; D010455:Peptides; D016875:tau Proteins; D012694:Serine; D000117:Acetylglucosamine