title: Phosphorylation modulates the local conformation and self-aggregation ability of a peptide from the fourth tau microtubule-binding repeat.
abstract: Phosphorylation of tau protein modulates both its physiological role and its aggregation into paired helical fragments, as observed in Alzheimer's diseased neurons. It is of fundamental importance to study paired helical fragment formation and its modulation by phosphorylation. This study focused on the fourth microtubule-binding repeat of tau, encompassing an abnormal phosphorylation site, Ser356. The aggregation propensities of this repeat peptide and its corresponding phosphorylated form were investigated using turbidity, thioflavin T fluorescence and electron microscopy. There is evidence for a conformational change in the fourth microtubule-binding repeat of tau peptide upon phosphorylation, as well as changes in aggregation activity. Although both tau peptides have the ability to aggregate, this is weaker in the phosphorylated peptide. This study reveals that both tau peptides are capable of self-aggregation and that phosphorylation at Ser356 can modulate this process.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, China.
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Du
authors.forename: Chun-Hui
authors.initials: CH
authors.lastname: Yu
authors.forename: Lian-Xiu
authors.initials: LX
authors.lastname: Zhou
authors.forename: Wei-Hui
authors.initials: WH
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Lei
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Zhao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011487:Protein Conformation; D020449:Repetitive Sequences, Amino Acid; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016875:tau Proteins