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In Silico Evaluation of Acetylation Mimics in the 27 Lysine Residues of Human Tau Protein

[ Vol. 16 , Issue. 5 ]

Author(s):

Yong-Chan Kim and Byung-Hoon Jeong*   Pages 379 - 387 ( 9 )

Abstract:


Background: Various neurodegenerative diseases, including Alzheimer’s disease (AD), are related to abnormal hyperphosphorylated 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 an acetylated tau is difficult.

Objective: Here, the authors 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, they also investigated 27 acetylation effects on the amyloid formation of tau proteins using Waltz.

Results: 15 acetylation mimics were estimated to be the most detrimental, which indicates that there may be novel pathogenic acetylation sites in the human tau protein. Interestingly, the deleterious effect of acetylation mimics was different according to the type of isoforms. Furthermore, all acetylation mimics were predicted to be a region of amyloid formation at the codons 274-279 of human tau protein. Notably, acetylation mimic of codon 311 (K311Q) induced the formation of an additional amyloid region located on codons 306-311 of the human tau protein.

Conclusion: To the best of our knowledge, this is the first simultaneous in-silico evaluation of the acetylation state of 27 human tau protein residues.

Keywords:

In-silico analysis, tau, Alzheimer's disease, acetylation, mimic, neurodegenerative diseases.

Affiliation:

Korea Zoonosis Research Institute, Chonbuk National University, Iksan, Jeonbuk 570-390, Korea Zoonosis Research Institute, Chonbuk National University, Iksan, Jeonbuk 570-390



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