Phosphorylation modulates the local conformation and self-aggregation ability of a peptide from the fourth tau microtubule-binding repeat.
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.
Du
Jin-Tang
JT
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing, China.
Yu
Chun-Hui
CH
Zhou
Lian-Xiu
LX
Wu
Wei-Hui
WH
Lei
Peng
P
Li
Yong
Y
Zhao
Yu-Fen
YF
Nakanishi
Hiroshi
H
Li
Yan-Mei
YM
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*
D016875:tau Proteins