7YES
The structure of EBOV L-VP35-RNA complex (state2)
Summary for 7YES
| Entry DOI | 10.2210/pdb7yes/pdb |
| EMDB information | 33776 |
| Descriptor | RNA-directed RNA polymerase L, VP35 of EBOV L-VP35 complex, ZINC ION (3 entities in total) |
| Functional Keywords | polymerase, complex, viral protein |
| Biological source | Ebola virus More |
| Total number of polymer chains | 5 |
| Total formula weight | 402886.86 |
| Authors | |
| Primary citation | Yuan, B.,Peng, Q.,Cheng, J.,Wang, M.,Zhong, J.,Qi, J.,Gao, G.F.,Shi, Y. Structure of the Ebola virus polymerase complex. Nature, 610:394-401, 2022 Cited by PubMed Abstract: Filoviruses, including Ebola virus, pose an increasing threat to the public health. Although two therapeutic monoclonal antibodies have been approved to treat the Ebola virus disease, there are no approved broadly reactive drugs to control diverse filovirus infection. Filovirus has a large polymerase (L) protein and the cofactor viral protein 35 (VP35), which constitute the basic functional unit responsible for virus genome RNA synthesis. Owing to its conservation, the L-VP35 polymerase complex is a promising target for broadly reactive antiviral drugs. Here we determined the structure of Ebola virus L protein in complex with tetrameric VP35 using cryo-electron microscopy (state 1). Structural analysis revealed that Ebola virus L possesses a filovirus-specific insertion element that is essential for RNA synthesis, and that VP35 interacts extensively with the N-terminal region of L by three protomers of the VP35 tetramer. Notably, we captured the complex structure in a second conformation with the unambiguous priming loop and supporting helix away from polymerase active site (state 2). Moreover, we demonstrated that the century-old drug suramin could inhibit the activity of the Ebola virus polymerase in an enzymatic assay. The structure of the L-VP35-suramin complex reveals that suramin can bind at the highly conserved NTP entry channel to prevent substrates from entering the active site. These findings reveal the mechanism of Ebola virus replication and may guide the development of more powerful anti-filovirus drugs. PubMed: 36171293DOI: 10.1038/s41586-022-05271-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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