Related Experiment Video
Updated: May 24, 2026

Advancing High-Resolution Imaging of Virus Assemblies in Liquid and Ice
Published on: July 20, 2022
Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus
Dongwen Zhou1, Suhman Chung, Maria Miller
1Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Abstract:
The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT) plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA hybrids. In addition, RNase H activity is required to precisely remove the RNA primers from nascent (-) and (+) strand DNA. We report here three crystal structures of the RNase H domain of xenotropic murine leukemia virus-related virus (XMRV) RT, namely (i) the previously identified construct from which helix C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with an active site α-hydroxytropolone inhibitor. Enzymatic assays showed that the intact RNase H domain retained catalytic activity, whereas the variant lacking helix C was only marginally active, corroborating the importance of this helix for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the essential role of helix C in binding a DNA/RNA hybrid and its likely mode of recognition. The crystal structure of the RNase H domain complexed with β-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor.
Related Concept Videos
Viruses with RNA Genomes
Size and Structure of Viral Genomes
Retrovirus Life Cycles
Retroviruses

