Structural characterization of the oligomerization of full-length Hantaan virus polymerase into symmetric dimers and hexamers
Hantaan virus is a dangerous human pathogen whose segmented negative-stranded RNA genome is replicated and transcribed by a virally-encoded multi-functional polymerase. Here we describe the complete cryo-electron microscopy structure of Hantaan virus polymerase in several oligomeric forms. Apo polymerase protomers can adopt two drastically different conformations, which assemble into two distinct homodimers, that can themselves gather to form hexamers. Polymerase dimerization induces the stabilization of most polymerase domains, including the C-terminal region that notably contains a C-terminal domain that contribute the most to dimers interface, along with a lariat region that participates to the polymerase steadying. Binding to viral RNA induces significant conformational changes resulting in oligomer disruption, suggesting the possible involvement of multimers as protecting systems that would stabilize the otherwise flexible C-terminal domains. Overall, these results provide new insights into the multimerization capability of Hantavirus polymerase and may help to define antiviral compounds to counteract these life-threatening viruses.