Lack of binding observed between human α-synuclein and Bcl-2 protein family

alpha -Synuclein is a presynaptic protein of unknown function that has been implicated in the pathogenesis of Parkinson's disease. To gain insight into the function of alpha -synuclein, the present study examined the association between alpha -synuclein and the following Bcl-2 family proteins: Bcl-2; Bcl-XL; Bcl-associated death promoter (BAD); and Bcl-2-associated X-protein. The results of a binding assay using gluthathione S-transferase (GST) fusion alpha -synuclein protein and an immunoprecipitation assay revealed that wild-type or mutant (A30P and A53T) alpha -synuclein (similar to 16 kDa) does not bind to any of these members of the Bcl-2 family. Furthermore, no binding was observed between alpha -synuclein and BAD, regardless of the phosphorylation state of the serine residue in BAD. In contrast, alpha -synuclein was observed to bind to synphilin-1. Although alpha -synuclein has been reported to bind to BAD, modification of alpha -synuclein might be required for such binding to occur. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.