Hepatitis C virus (HCV) core protein forms the internal viral coat tha
t encapsidates the genomic RNA and is enveloped in a host cell-derived
lipid membrane. As the single capsid protein, core should be capable
of multimerization but attempts to produce virus-like particles follow
ing expression of HCV structural proteins have not been successful. In
this study, we have analysed the interaction capacity of full-length
and truncated HCV core using the yeast two-hybrid system. Full-length
core containing or tacking the translocation signal for the El glycopr
otein did not interact with full-length or truncated core proteins. Tr
uncation to the N-terminal 122 aa revealed an interaction domain which
was mapped to the tryptophan-rich sequence from aa 82-102 and was ter
med the main homotypic interaction domain. The C-terminal hydrophobic
fragment of core (aa 122-172) was incapable of interacting with itself
but interacted with the main homotypic interaction domain in trans (t
he weak heterotypic interaction domain). Core proteins truncated at th
eir N and C termini (aa 46-102) were trans-activating when fused to th
e DNA-binding domain of GAL4. Based on our results, we suggest that th
e C-terminal segment may interact in cis with the main homotypic inter
action domain and thereby prevent multimerization. Core-core interacti
on was also observed for in vitro-translated proteins bound to truncat
ed immobilized core102. However, interaction was less specific in this
system suggesting that protein interaction and possibly conformationa
l alteration of core may be dependent on the experimental system.