PrPC interacts with potassium channel tetramerization domain containing 1 (KCTD1) protein through the PrP51-136 region containing octapeptide repeats

Abstract To identify molecular interaction partners of the cellular prion protein (PrP C ), we applied a yeast two-hybrid screen on a bovine brain cDNA expression library and identified the potassium channel tetramerization domain containing 1 (KCTD1) as a PrP C interacting protein. Deletion mapping showed that PrP C specifically binds KCTD1 through the unstructured PrP 51-136 region. We further confirmed the interaction between PrP C and KCDT1 protein by co-immunoprecipitation in vivo and by a biosensor assay in vitro . Interestingly, the binding of an insertion mutant PrP 8OR to KCTD1 is higher than that of wild-type PrP C , suggesting an important role for an unstructured region harboring octapeptide repeats in the KCTD1-PrP C interaction. Our results identify a novel PrP C -interacting protein and suggest a new approach to investigating the unidentified physiological cellular function of PrP C .