title: Mechanism of BAG1 repair on Parkinson's disease-linked DJ1 mutation.
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.
authors.affiliation: China Medical University Beigang Hospital, Yunlin, Taiwan.
authors.forename: Calvin Yu-Chian
authors.initials: CY
authors.lastname: Chen
mesh_terms: D001665:Binding Sites; D003553:Cystine / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009154:Mutation; D015513:Oncogene Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D014157:Transcription Factors; D003553:Cystine; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1