title: O-GlcNAcylation modulates the self-aggregation ability of the fourth microtubule-binding repeat of tau.
abstract: 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.
authors.affiliation: Department of Chemistry, Beihua University, Jilin 132013, PR China.
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Yu
authors.forename: Tong
authors.initials: T
authors.lastname: Si
authors.forename: Wei-Hui
authors.initials: WH
authors.lastname: Wu
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Du
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Li
mesh_terms: 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*
chemical_list: C054369:MAPT protein, human; D010455:Peptides; D016875:tau Proteins; D012694:Serine; D000117:Acetylglucosamine