Hepatitis C virus core protein plays an important role in the assembly and packaging of the viral genome. We have studied the structure of the N-terminal half of the core protein (C82) which was shown to be sufficient for the formation of nucleocapsid-like particle (NLP) in vitro and in yeast. Structural bioinformatics analysis of C82 suggests that it-is mostly unstructured. Circular dichroism and structural NMR data indicate that C82 lacks secondary structure. Moreover, NMR relaxation data shows that C82 is highly disordered. These results indicate that the N-terminal half of the HCV core protein belongs to the growing family of intrinsically unstructured proteins (IUP). This explains the tendency of the hepatitis C virus core protein to interact with several host proteins, a well-documented characteristic of IUPs. (C) 2008 Elsevier Inc. All rights reserved.