Mechanism of BAG1 repair on Parkinson's disease-linked DJ1 mutation

Journal of Biomolecular Structure & Dynamics
Calvin Yu-Chian Chen

Abstract

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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Citations

Oct 19, 2012·Journal of Biomolecular Structure & Dynamics·Kuan-Chung ChenCalvin Yu-Chian Chen
Nov 14, 2012·Journal of Biomolecular Structure & Dynamics·Kuan-Chung ChenCalvin Yu-Chian Chen
Jun 26, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Hung-Jin HuangCalvin Yu-Chian Chen
May 31, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Yung An TsouCalvin Yu-Chian Chen
Jan 21, 2015·Journal of Molecular Neuroscience : MN·Zhenhai SongQinghua Zhang
Feb 14, 2015·Computational Biology and Chemistry·Maad Shatnawi, Nazar Zaki
Jan 11, 2014·Journal of Biomolecular Structure & Dynamics·Nejla StambouliAmel Ben Ammar Elgaaied
Dec 19, 2013·International Journal of Genomics·Xiao-Yang LiaoYu Liu

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Methods Mentioned

BETA
ubiquitination

Software Mentioned

ZDock
iTasser
TASSER
Build Mutants from Discovery Studio
CHARMm
DS2
Dock
iScreen

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