Phosphorylation by Par-1/MARK2 on KXGS motifs in the microtubule-binding domain of tau has been shown to be required for initiation of the pathogenic cascade of hyperphosphorylation, which is ultimately associated with NFT formation in tauopathies [ 29].
Previously, it has been shown that the key regions responsible for tau tau interactions are located in the microtubule-binding domain of tau [ 37, 64, 65]; however, their pathologic gain of function is regulated by the truncation of distant parts of the tau protein molecule [ 27].
Synthetic peptides representing each of the four microtubule-binding domains of tau more avidly bind ApoE3 than ApoE4.
The repeats and some adjoining sequences constitute the microtubule-binding domains of tau [ 12].
The mutations are mainly clustered in the five most 3′ exons from 9 to 13, encoding the four microtubule-binding domains of tau.
Khrapunov, S. et al. Unusual characteristics of the DNA binding domain of epigenetic regulatory protein MeCP2 determine its binding specificity.
With this knowledge, we developed a tau peptide vaccine encompassing the structural determinant derived from the mis-disordered second microtubule-binding repeat domain of tau.
We have shown previously that it binds the microtubule binding domains of the microtubule-associated proteins, MAP2, MAP4, and tau.
Interestingly, HEK cells overexpressing this tau construct formed aggregates which were released and internalized by other HEK cells [ 50], providing direct evidence that microtubule-binding domain fragments of tau aggregates can be transferred between cells in vitro.
Structural studies show interaction modes of Hsp90 with the intrinsically disordered Alzheimer's disease-causing protein Tau, the kinase Cdk4 in a partially unfolded state and the folded ligand-binding domain of a steroid receptor.
