PubMed: 17493042

Title
Structural principles of tau and the paired helical filaments of Alzheimer's disease.
Journal
Brain pathology (Zurich, Switzerland)
Volume
17
Issue
None
Pages
83-90
Date
2007-01-01
Authors
Biernat J | Mandelkow E | Mandelkow EM | von Bergen M

Evidence b46cbf4a15

Tau binds to microtubule through the C-terminal repeat domain and 4R bind more tightly than 3R, while phosphorylation, especially of the repeat domain tends to decrease binding.

Evidence 8be7abfe46

A further potent detaching site is phosphoS214, which can be phosphorylated by PKA and other kinases of the AGC group (PKA/PKG/PKC group of protein kinases), and is up-regulated during mitosis (16, 63). Tau contains one or two cysteines in the repeat domain (C291 in R2, present in 4R isoforms, and C322 in R3), which can be engaged in intra- or intermolecular cross-linking affecting conformation, dimerization and aggregation (108).

Evidence 2c2795cba6

Two hexapeptide motifs at the beginning of R2 and R3 promote paired helical filament (PHF) aggregation by inducing β-structure.

Evidence f1a8401428

Tyrosine kinases target Y18 [fyn, (79)] and Y394 [abl, (31)].

Evidence 4d4f43ecc7

The lysine-isoleucine-glycineserine motif (KIGS) or lysine-cysteineglycine-serine motif (KCGS) motifs in the repeat domain (S262, S293, S324, S356) can be phosphorylated by MARK, PKA, SAD kinases, CaMKII and p70S6K, which strongly reduces the tau microtubule interactions (36, 74, 96), [note that phosphorylation at these sites also inhibits tau aggregation, illustrating an analogous role for the repeat domain in the physiological and pathological functions of tau (106)].

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