Prion diseases are progressive, infectious neurodegenerative disorders caused primarily by the misfolding of the cellular prion protein, PrP(c) , into an insoluble, protease-resistant, aggregated isoform termed PrP(sc) . In native conditions, PrP(c) has a structured C-terminal domain and a highly flexible N-terminal domain. A part of this N-terminal domain consists of 4-5 repeats of an unusual glycine rich, eight amino acids long peptide known as the octapeptide repeat (OR) domain. In this paper, we successfully report the first crystal structure of an octapeptide repeat of PrP(c) bound to the POM2 Fab antibody fragment. The structure was solved at a resolution of 2.3 Å by molecular replacement. While several studies have previously predicted a β-turn like structure of the unbound octapeptide repeats, our structure shows an extended conformation of the octapeptide repeat when bound to a molecule of the POM2 Fab indicating that the bound Fab disrupts any putative native β turn conformation of the octapeptide repeats. Encouraging results from several recent studies have shown that administering small molecule ligands or antibodies targeting the OR domain of PrP result in arresting the progress of peripheral prion infections both in ex vivo and in in vivo models. This makes the structural study of the interactions of POM2 Fab with the OR domain very important as it would help us to design smaller and tighter binding OR ligands.