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First crystal structure of a nonstructural hepatitis E viral protein identifies a putative novel zinc-binding protein

Proudfoot, Andrew, Hyrina, Anastasia, Holdorf, Meghan, Frank, Andreas and Bussiere, Dirksen (2019) First crystal structure of a nonstructural hepatitis E viral protein identifies a putative novel zinc-binding protein. Journal of Virology, 93 (13). ISSN 10985514


Hepatitis E virus (HEV) is a 7.2-kb positive-sense, single-stranded RNA virus containing three partially overlapping reading frames, ORF1 to ORF3. All nonstructural proteins required for viral replication are encoded by ORF1 and are transcribed as a single transcript. Computational analysis of the complete ORF1 polyprotein identified a previously uncharacterized region of predicted secondary structure bordered by two disordered regions coinciding partially with a region predicted as a putative cysteine protease. Following successful cloning, expression, and purification of this region, the crystal structure of the identified protein was determined and identified to have considerable structural homology to a fatty acid binding domain. Further analysis of the structure revealed a metal binding site, shown unambiguously to specifically bind zinc via a nonclassical, potentially catalytic zinc-binding motif. Based on the structural homology of the HEV protein with known structures, along with the presence of a catalytic zinc-binding motif, it is possible that the identified protein corresponds to the HEV protease, which could require activation or repression through the binding of a fatty acid. This represents a significant step forward in the characterization and the understanding of the molecular mechanisms of the HEV genome. We present analysis for the first time of this identified nonstructural protein, expanding the knowledge and understanding of the complex mechanisms of HEV biology.

Item Type: Article
Keywords: Biophysics Crystal structure Fatty-acid binding Nuclear magnetic resonance Protease
Date Deposited: 03 Aug 2021 00:45
Last Modified: 03 Aug 2021 00:45


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