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α-Synuclein can be degraded by both the ubiquitin-proteasomal system and the chaperone-lysosomal system. However, the switching mechanism between the two pathways is not clearly understood. In our study, we investigated the mutual association between the binding of α-synuclein to heat shock cognate 70 and the lysosomal translocation of α-synuclein. Tyrosine phosphorylation of Y136 on α-synuclein increased when it bound to heat shock protein 70. We also found that tyrosine phosphorylation of α-synuclein can be regulated by focal adhesion kinase pp125 and protein tyrosine phosphatase 1B. Furthermore, protein tyrosine phosphatase 1B inhibitor protected dopaminergic neurons against cell death and rescued rotarod performance in a Parkinson's disease animal model. This study provides evidence that the regulation of Y136 phosphorylation of α-synuclein can improve behavioral performance and protect against neuronal death by promoting the turnover of lysosomal degradation of α-synuclein. As a result, protein tyrosine phosphatase 1B inhibitor may be used as a potential therapeutic agent against Parkinson's disease.
Pubmed ID: 22776201
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It is a web-server that can be used to explore protein interfaces and predict protein-protein interactions. It is a website for protein interface analysis and prediction of putative protein-protein interactions. It is composed of a database holding protein interface structures derived from the Protein Data Bank (PDB). The server also includes summary information about related proteins and an interactive protein interface viewer. A list of putative protein-protein interactions obtained by running our prediction algorithm can also be accessed. These results are applied to a set of protein structures obtained from the PDB at the time of algorithm execution. Users can browse through the non-redundant dataset of representative interfaces on which the prediction algorithm depends, retrieve the list of similar structures to these interfaces or see the results of interaction predictions for a particular protein. Another service provided is interactive prediction. This is done by running the algorithm for user input structures.
View all literature mentionsA database of predicted human protein-protein interactions. The predictions have been made using a naïve Bayesian classifier to calculate a Score of interaction. There are 37606 interactions with a Score ≥1 indicating that the interaction is more likely to occur than not to occur.
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