ASIA unversity:Item 310904400/23387
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    题名: Mechanism of BAG1 Repair on Parkinson's Disease Linked-DJ1 Mutation,
    作者: 陳語謙;Chen, Calvin Yu-Chian
    贡献者: 生物科技學系
    关键词: protein-protein interaction;BAG1;molecular dynamics;protein repair;Parkinson’s disease
    日期: 2012
    上传时间: 2012-12-10 11:39:25 (UTC+8)
    摘要: Mutant oncogene DJ1 L166P has been linked to a familial form of early-onset Parkinson's disease (PD). The DJ1 mutant deformed C-terminal helices and prevented the formation of a functional DJ1 dimer. Intriguingly, chaperon modulator, BCL2-associated athanogene (BAG1), has been shown to repair DJ1 mutant and restore its functions. Molecular simulation techniques were employed to elucidate protein-protein interactions between BAG1 and DJ1. Interaction of BAG1 with DJ1 showed recovery of disrupted alpha helix structures and H-bonds stabilizing the functional site Cys106. The His126-Pro184 H-bond (hydrogen-bond) critical to maintaining dimer interfaces was also restored and led to the restoration of dimer formation. High conformational to functional DJ1 dimer was confirmed root mean square deviation = 0.74 Å). Results of this suggest several molecular insights on BAG1-DJ1 repair mechanism and may have an impact on advancing PD treatments.
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