6e5x | pdb_00006e5x
Crystal structure of Ebola virus VP30 C-terminus/RBBP6 peptide complex
Structural highlights
Function[VP30_EBOZ5] Acts as a transcription anti-termination factor immediately after transcription initiation, but does not affect transcription elongation. This function has been found to be dependent on the formation of an RNA stem-loop at the transcription start site of the first gene. Binds to RNA (By similarity). [RBBP6_HUMAN] E3 ubiquitin-protein ligase which promotes ubiquitination of YBX1, leading to its degradation by the proteasome. May play a role as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in increase of MDM2-mediated ubiquitination and degradation of p53/TP53; may function as negative regulator of p53/TP53, leading to both apoptosis and cell growth. Publication Abstract from PubMedEbola 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. Protein Interaction Mapping Identifies RBBP6 as a Negative Regulator of Ebola Virus Replication.,Batra J, Hultquist JF, Liu D, Shtanko O, Von Dollen J, Satkamp L, Jang GM, Luthra P, Schwarz TM, Small GI, Arnett E, Anantpadma M, Reyes A, Leung DW, Kaake R, Haas P, Schmidt CB, Schlesinger LS, LaCount DJ, Davey RA, Amarasinghe GK, Basler CF, Krogan NJ Cell. 2018 Dec 13;175(7):1917-1930.e13. doi: 10.1016/j.cell.2018.08.044. PMID:30550789[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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