The smallest of the four genes encoded in the Hepatitis B virus (HBV) genome, codes for a protein that is 154 aa long, which has been shown to be essential for the infectivity and pathogenesis of HBV. Though this protein has been shown to regulate various processes in the cell, such as DNA damage repair, apoptosis and cell proliferation, as well as interact with a large number of host target proteins, its molecular structure and mechanism are presently unknown. Our work shows that it is a metalloprotein carrying an unprecedented [Fe-S] cofactor. The ligands to the cluster have been interrogated via site directed mutagenesis, and are arranged in an unprecedented binding motif. The cluster undergoes a reversible redox inter-conversion to higher nuclearity [Fe-S] cofactors. The integrity and role of the cluster promoting the function of this multi-faceted protein are presented. This work provides the first evidence for the presence, function of the metallocluster in the HBV-associated protein and the manner by which the latter may contribute to promoting HBV carcinogenesis.

Unprecedented [FeS] cluster in the core of the hepatitis B infection

253rd National Meeting (2017)

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