Title

Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity.

Journal

The Biochemical journal

Volume

462

Issue

None

Pages

77-88

Date

2014-08-15

Authors

Clark DJ | Cooper GL | Funk KE | Kuret J | Liao Z | Schafer KN | Thomas SN | Yang AJ

An example of a spectrum identifying K311 as a site of dimethylation at 2.2 ppm mass accuracy is shown in Fig. 2B. This residue was reported as a possible methylation site in AD-brain derived tau protein on the basis of Edman degradation years ago [36]. It resides within the “PHF6” motif of the MTBR, which has been reported to mediate the aggregation propensity of recombinant monomeric tau in vitro [6, 37]. Other methylation sites within the MTBR include K259, K290, and K353, each of which lies in a KXGS motif associated with AMP-activated protein kinase mediated regulation of microtubule binding [38]. Within the N-terminal projection domain, Lys methylation was detected at K24, K44, K67, and K190 (Fig. 1).

These data indicate that Lys methylation depressed the intrinsic aggregation propensity of tau, and did so in part by increasing the concentration of tau needed to support fibril formation.

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.