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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Cystine / chemistry
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism
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Humans
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Hydrogen Bonding
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Intracellular Signaling Peptides and Proteins / chemistry*
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Intracellular Signaling Peptides and Proteins / genetics*
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Intracellular Signaling Peptides and Proteins / metabolism
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Molecular Dynamics Simulation
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Mutation*
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Oncogene Proteins / chemistry*
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Oncogene Proteins / genetics*
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Oncogene Proteins / metabolism
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Parkinson Disease / genetics*
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Parkinson Disease / metabolism
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Protein Binding
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Protein Deglycase DJ-1
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Protein Interaction Domains and Motifs
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Protein Multimerization
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Protein Structure, Secondary
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Reproducibility of Results
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Transcription Factors / chemistry*
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Transcription Factors / metabolism
Substances
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BCL2-associated athanogene 1 protein
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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Oncogene Proteins
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Transcription Factors
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Cystine
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PARK7 protein, human
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Protein Deglycase DJ-1