Prions are fatal neurodegenerative transmissible agents causing several incurable illnesses in humans and animals. Prion diseases are caused by the structural conversion of the cellular prion protein, PrPC, into its misfolded oligomeric form, known as prion or PrPSc. The canonical human PrPC (HuPrP) fold features an unstructured N-terminal part (residues 23-124) and a well-defined C-terminal globular domain (residues 125-231). Compelling evidence indicates that an evolutionary N-terminal conserved motif AGAAAAGA (residues 113-120) plays an important role in the conversion to PrPSc. The intrinsic flexibility of the N-terminal has hampered efforts to obtain detailed atomic information on the structural features of this palindromic region. In this study, we crystallized the full-length HuPrP in complex with a nanobody (Nb484) that inhibits prion propagation. In the complex, the prion protein is unstructured from residue 23 to 116. The palindromic motif adopts a stable and fully extended configuration to form a three-stranded antiparallel beta-sheet with the beta 1 and beta 2 strands, demonstrating that the full-length HuPrP(C) can adopt a more elaborate beta 0-beta 1-alpha 1-beta 2-alpha 2-alpha 3 structural organization than the canonical beta 1-alpha 1-beta 2-alpha 2-alpha 3 prion-like fold. From this structure, it appears that the palindromic motif mediates beta-enrichment in the PrPC monomer as one of the early events in the conversion of PrPC into PrPSc.