Hepatitis B Virus X Protein Function Requires Zinc Binding

作者：Dhivya Ramakrishnan, Weimei Xing, Rudolf K. Beran, Saketh Chemuru, Henry W. Rohrs, Anita Niedziela‐Majka, Bruno Marchand, Upasana Mehra, Aleš Zábranský, Michal Doležal, Martin Hubálek, Iva Pichová, Michael L. Gross, Hyock Joo Kwon, Simon P. Fletcher · 发表于：Journal of Virology · 年份：2019 · DOI：10.1128/jvi.00250-19 · 被引用次数：48 · 研究领域：Hepatitis B Virus Studies、Hepatitis C virus research、Viral Infections and Outbreaks Research

The structural maintenance of chromosomes 5/6 complex (Smc5/6) is a host restriction factor that suppresses HBV transcription. HBV counters this restriction by expressing HBV X protein (HBx), which redirects a host ubiquitin ligase to target Smc5/6 for degradation. Despite this recent advance in understanding HBx function, the key regions and residues of HBx required for Smc5/6 degradation have not been determined. In the present study, we performed biochemical, biophysical, and cell-based analyses of HBx. By doing so, we mapped the minimal functional region of HBx and identified a highly conserved CCCH motif in HBx that is likely responsible for coordinating zinc and is essential for HBx function. We also developed a method to produce soluble recombinant HBx protein that likely adopts a physiologically relevant conformation. Collectively, this study provides new insights into the HBx structure-function relationship and suggests a new approach for structural studies of this enigmatic viral regulatory protein.