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Int J Biol Sci 2007; 3(1):1-7. doi:10.7150/ijbs.3.1

Research Paper

Effect of Reparation of Repeat Sequences in the Human α-Synuclein on Fibrillation Ability

Koji Sode, Sayaka Ochiai, Natsuki Kobayashi, Eri Usuzaka

Department of Biotechnology, Graduate School of Engineering, Tokyo University of Agriculture & Technology, 2-2-4-16, Nakacho, Koganei, Tokyo 184-8588, Japan

Abstract

The aggregation and fibrillation of α-synuclein has been implicated as a causative factor in the Parkinson's disease. The hexamer motif KTKEGV is found in each of the seven imperfect repeat sequences in the N-terminal half of α-synuclein. The motif is not fully conserved in the sixth and seventh repeats. We created mutants in which the motif was repaired to be fully conserved in either (Rep6 and Rep7) or both (Rep67) of these two repeats. The Rep6 and Rep67 mutants showed a greatly reduced propensity to aggregate and fibrillate while all three mutants showed greater resistance to HFIP-induced formation of the α-helix intermediate. Resistance to formation in the partially folded intermediate may repress the folding of α-synuclein, consequently interfering with the aggregation and fibril formation. These results demonstrated that KTKEGV repeats may have a significant role in keeping native unfolded status of α-synuclein.

Keywords: α-synuclein, aggregation and fibrillation, site-directed mutagenesis, natively unfolded protein, NAC region, 11-residue repeat sequences

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How to cite this article:
Sode K, Ochiai S, Kobayashi N, Usuzaka E. Effect of Reparation of Repeat Sequences in the Human α-Synuclein on Fibrillation Ability. Int J Biol Sci 2007; 3(1):1-7. doi:10.7150/ijbs.3.1. Available from http://www.ijbs.com/v03p0001.htm