Page 16 - L. Genetics and genomics

[L. Genetics and genomics-15]

In silico evaluation of acetylation mimics in the 27 lysine

residues of human tau protein

Yong-Chan Kim¹˙², Byung-Hoon Jeong¹˙²

¹Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju 54896, South Korea, ²Korea

Zoonosis Research Institute , Jeonbuk National University, Iksan 54531, South Korea

Various neurodegenerative diseases, including Alzheimer’s disease (AD), are related to abnormal hyper-
phosphorylated microtubule-associated protein tau accumulation in brain lesions. Recent studies have focused on

toxicity caused by another post-translational modification (PTM), acetylation of the lysine (K) residues of tau protein.

Because there are numerous acetylation sites, several studies have introduced mimics of tau acetylation using amino
acid substitutions from lysine to glutamine (Q). However, human tau protein contains over 20 acetylation sites; thus,
investigation of the effects of acetylated tau is difficult. Here, we in silico evaluated acetylation effects using SIFT,

PolyPhen-2 and PROVEAN which can estimate the effects of amino acid substitutions based on the sequence
homology or protein structure in tau isoforms. In addition, we also investigated 27 acetylation effects on amyloid

formation of tau protein using Waltz. 15 acetylation mimics were estimated to be most detrimental, which indicates
that there may be novel pathogenic acetylation sites in human tau protein. Interestingly, deleterious effect of

acetylation mimics was different according to type of isoforms. Furthermore, all acetylation mimics were predicted
to be region of amyloid formation at the codons 274-279 of human tau protein. Notably, acetylation mimic of

codon 311 (K311Q) induced formation of additional amyloid region located on codons 306-311 of human tau
protein. To the best of our knowledge, this is the first simultaneous in-silico evaluation of the acetylation state of

27 human tau protein residue.