Prions are fatal neurodegenerative transmissible agents causing many diseases (e.g. Creutzfeldt-Jakob disease in human, spongiform encephalopathy in bovine and scrapie in sheep). The structural investigation of prions is challenging due to the protein intrinsic disorder (mostly located in the N-terminal region). We used PrP specific nanobodies derived from Camelid antibodies to determine the structure of full-length mouse PrPC (23–230) by x-ray crystallography. Initial attempts to co-crystallize full-length mouse PrPC in complex with Nb484 did not produce crystals. However, limited *in-situ* proteolysis produced plate-like crystals which diffracted to 2.7 Å resolution. Here we report the characterization at molecular level of the interaction of mouse PrPC and a nanobody (Nb484).
Our goal is to use nanobodies as a molecular tool to obtain a better understanding of the mechanism of the amyloidogenic disease formation. We also crystallized Nb484 alone and collected a complete dataset at high resolution (1.2 Å). Our experiments suggest that the nanobodies can be used as a molecular tool by helping the crystallization and by inhibiting the PrPC to PrPSc transition.