7YET

The structure of EBOV L-VP35 in complex with suramin

7YET の概要

• エントリーDOI: 10.2210/pdb7yet/pdb
• EMDBエントリー: 33777
• 分子名称: RNA-directed RNA polymerase L, Polymerase cofactor VP35, 8,8'-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFON IC ACID (3 entities in total)
• 機能のキーワード: polymerase, complex, viral protein
• 由来する生物種: Ebola virus; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 404118.73

構造登録者

Shi, Y.,Yuan, B.,Peng, Q. (登録日: 2022-07-06, 公開日: 2022-10-05, 最終更新日: 2025-06-25)

主引用文献

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

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: 36171293
DOI: 10.1038/s41586-022-05271-2

実験手法

ELECTRON MICROSCOPY (3.3 Å)