Protein Interaction Mapping Identifies RBBP6 as a Negative Regulator of Ebola Virus Replication

被引：135

作者：

Batra, Jyoti ^{[1
,3
,4
]}

Hultquist, Judd F. ^{[2
,3
,4
,5
]}

Liu, Dandan ^{[6
]}

Shtanko, Olena ^{[7
]}

Von Dollen, John ^{[2
,3
,4
]}

Satkamp, Laura ^{[2
,3
,4
]}

Jang, Gwendolyn M. ^{[2
,3
,4
]}

Luthra, Priya ^{[1
]}

Schwarz, Toni M. ^{[8
]}

Small, Gabriel I. ^{[6
]}

Arnett, Eusondia ^{[9
]}

Anantpadma, Manu ^{[7
,11
]}

Reyes, Ann ^{[7
]}

Leung, Daisy W. ^{[6
]}

Kaake, Robyn ^{[2
,3
,4
]}

Haas, Paige ^{[2
,3
,4
]}

Schmidt, Carson B. ^{[2
,3
,4
]}

Schlesinger, Larry S. ^{[9
]}

LaCount, Douglas J. ^{[10
]}

Davey, Robert A. ^{[7
,11
]}

Amarasinghe, Gaya K. ^{[6
]}

Basler, Christopher F. ^{[1
]}

Krogan, Nevan J. ^{[2
,3
,4
]}

机构：

[1] Georgia State Univ, Inst Biomed Sci, Ctr Microbial Pathogenesis, Atlanta, GA 30303 USA

[2] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Quantitat Biosci Inst, San Francisco, CA 94158 USA

[4] J David Gladstone Inst, San Francisco, CA 94158 USA

[5] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA

[6] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63105 USA

[7] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX 78245 USA

[8] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[9] Texas Biomed Res Inst, San Antonio, TX 78245 USA

[10] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA

[11] Boston Univ, Sch Med, Dept Microbiol, NEIDL, Boston, MA 02118 USA

来源：

CELL | 2018年 / 175卷 / 07期

关键词：

DOUBLE-STRANDED-RNA; VP35; PROTEIN; VIRAL-TRANSCRIPTION; KARYOPHERIN; REVEALS; SYSTEM; BINDS; PACT; PHOSPHORYLATION; OLIGOMERIZATION;

D O I：

10.1016/j.cell.2018.08.044

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：1917 / +

页数：27

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