6E5X

Crystal structure of Ebola virus VP30 C-terminus/RBBP6 peptide complex

6E5X の概要

• エントリーDOI: 10.2210/pdb6e5x/pdb
• 分子名称: Minor nucleoprotein VP30, E3 ubiquitin-protein ligase RBBP6, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: viral protein
• 由来する生物種: Zaire ebolavirus (strain Kikwit-95) (ZEBOV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16060.77

構造登録者

Liu, D.,Small, G.I.,Leung, D.W.,Amarasinghe, G.K. (登録日: 2018-07-23, 公開日: 2018-12-12, 最終更新日: 2023-10-11)

主引用文献

Batra, J.,Hultquist, J.F.,Liu, D.,Shtanko, O.,Von Dollen, J.,Satkamp, L.,Jang, G.M.,Luthra, P.,Schwarz, T.M.,Small, G.I.,Arnett, E.,Anantpadma, M.,Reyes, A.,Leung, D.W.,Kaake, R.,Haas, P.,Schmidt, C.B.,Schlesinger, L.S.,LaCount, D.J.,Davey, R.A.,Amarasinghe, G.K.,Basler, C.F.,Krogan, N.J.
Protein Interaction Mapping Identifies RBBP6 as a Negative Regulator of Ebola Virus Replication.
Cell, 175:1917-1930.e13, 2018

PubMed Abstract: Ebola virus (EBOV) infection often results in fatal illness in humans, yet little is known about how EBOV usurps host pathways during infection. To address this, we used affinity tag-purification mass spectrometry (AP-MS) to generate an EBOV-host protein-protein interaction (PPI) map. We uncovered 194 high-confidence EBOV-human PPIs, including one between the viral transcription regulator VP30 and the host ubiquitin ligase RBBP6. Domain mapping identified a 23 amino acid region within RBBP6 that binds to VP30. A crystal structure of the VP30-RBBP6 peptide complex revealed that RBBP6 mimics the viral nucleoprotein (NP) binding to the same interface of VP30. Knockdown of endogenous RBBP6 stimulated viral transcription and increased EBOV replication, whereas overexpression of either RBBP6 or the peptide strongly inhibited both. These results demonstrate the therapeutic potential of biologics that target this interface and identify additional PPIs that may be leveraged for novel therapeutic strategies.

PubMed: 30550789
DOI: 10.1016/j.cell.2018.08.044

実験手法

X-RAY DIFFRACTION (1.5 Å)