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

To identify molecular interaction partners of the cellular prion protein (PrPC), 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 PrPC interacting protein. Deletion mapping showed that PrPC specifically binds KCTD1 through the unstructured PrP51-136 region. We further confirmed the interaction between PrPC and KCDT1 protein by co-immunoprecipitation in vivo and by a biosensor assay in vitro. Interestingly, the binding of an insertion mutant PrP8OR to KCTD1 is higher than that of wild-type PrPC, suggesting an important role for an unstructured region harboring octapeptide repeats in the KCTD1-PrPC interaction. Our results identify a novel PrPC-interacting protein and suggest a new approach to investigating the unidentified physiological cellular function of PrPC.

► We identified PrPC interacts with KCTD1 protein through PrP51-136 by a yeast two-hybrid. ► And co-immunoprecipitation confirmed the interaction in vivo. ► A biosensor assay showed the binding of an insertion mutant PrP8OR to KCTD1 is higher than that of wild type PrPC.