1) Replication and transcription of influenza virus genome mainly depend on its RNA-dependent RNA polymerase (RdRP), composed of the PA, PB1, and PB2 subunits. Although extensively studied, the underlying mechanism of the RdRP complex is still unclear. Using single-particle cryo-electron microscopy, we have reconstructed the RdRP tetramer complex at 4.3 Å, highlighting the assembly and interfaces between monomers within the tetrameric structure.
2) Toll-like receptors (TLRs) have crucial roles in innate immunity, functioning as pattern-recognition receptors. TLR13 recognizes a conserved sequence from bacterial 23S rRNA and then triggers an immune response. In a collaboration work with Prof. Jiawei Wang and Jijie Chai at Tsinghua University, we developed a new set of approaches to solve the phasing problem of X-ray crystallography structural determination of the TLR13-RNA complex (300kDa as a dimer) using single particle cryo-EM reconstruction. My lab obtained the complex’s cryo-EM structure at 5 Å resolution and Prof. Jiawei Wang solved the crystal structure at 2.5 Å resolution using the EM map as initial phase information. This work was a very nice synergetic combination of X-ray crystallography with cryo-EM in structural biology and evealed important insights into innate immunity.