9XSC
Cryo-EM structure of cchfv apo-state
Summary for 9XSC
| Entry DOI | 10.2210/pdb9xsc/pdb |
| EMDB information | 67173 |
| Descriptor | RNA-directed RNA polymerase L (1 entity in total) |
| Functional Keywords | rna-binding protein, rna binding protein |
| Biological source | Crimean-Congo Hemorrhagic Fever virus strain China |
| Total number of polymer chains | 1 |
| Total formula weight | 452401.06 |
| Authors | |
| Primary citation | Li, M.,Zhu, K.,Liu, Y.,Shang, K.,Li, Y.,Wang, X.,Wang, J.,Jia, J.,Ai, X.,Ni, D.,Cui, S.,Zhu, H.,Gao, X. Structures of the Crimean-Congo hemorrhagic fever virus RNA-dependent RNA polymerase. Cell Discov, 12:-, 2026 Cited by PubMed Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV), designated by the WHO as a priority pathogen under its R&D Blueprint for emerging epidemics, poses a major global health threat, yet licensed vaccines or specific antiviral treatments are lacking. As the sole viral enzyme responsible for genome replication and transcription, the CCHFV L protein is a large, multienzymatic protein, but its exceptional size (> 450 kDa) and extensive domain architecture have hindered structural analysis. Here, we present high-resolution cryo-electron microscopy structures of the full-length CCHFV L protein in its apo state and bound to the 5' viral RNA promoter. These structures reveal the largest polymerase known among Bunyavirales and demonstrate that the apo form adopts a highly flexible conformation in which multiple functional elements remain disordered. Binding of the 5' promoter RNA triggers extensive conformational rearrangements that organize these elements into a catalytically competent active site. We define a conserved 5' hook-binding mode and identify two previously unrecognized residues (K1545 and E1637) that form a constriction at the NTP entry channel, representing newly defined regulatory motifs J and K conserved across Bunyavirales. We further characterize an expanded pendant domain unique to nairoviruses that, although not essential for promoter binding, likely modulates template movement within the internal tunnel during RNA synthesis. Our results provide the first structural framework for a nairovirus polymerase, illuminate the mechanisms of CCHFV RNA synthesis, and establish a foundation for structure-guided antiviral development against this high-priority pathogen. PubMed: 42443146DOI: 10.1038/s41421-026-00905-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.85 Å) |
Structure validation
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