The Ebola Virus VP30-NP Interaction Is a Regulator of Viral RNA Synthesis.
The Ebola Virus VP30-NP Interaction Is a Regulator of Viral RNA Synthesis.
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DOI：
10.1371/journal.ppat.1005937
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发表时间：
2016-10
期刊：
影响因子：
6.7
通讯作者：
Saphire EO
中科院分区：
文献类型：
--
作者：
Kirchdoerfer RN;Moyer CL;Abelson DM;Saphire EO
Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays. We have found that the VP30 C-terminal domain interacts with a short peptide in the C-terminal region of NP. Further, we have solved crystal structures of the VP30-NP complex for both Ebola and Marburg viruses. These structures reveal that a conserved, proline-rich NP peptide binds a shallow hydrophobic cleft on the VP30 C-terminal domain. Structure-guided Ebola virus VP30 mutants have altered affinities for the NP peptide. Correlation of these VP30-NP affinities with the activity for each of these mutants in a cell-based mini-replicon assay suggests that the VP30-NP interaction plays both essential and inhibitory roles in Ebola virus RNA synthesis. Filoviruses use a system of proteins and RNA to regulate viral RNA genome transcription and replication. Here, we have determined crystal structures and the biological functions of the protein complex formed by the filovirus transcriptional activator, VP30, and the core component of the nucleocapsid machinery, NP. The complex of these two essential players represses Ebola virus RNA synthesis and may have played a role in the evolution of filoviruses to tune viral RNA synthesis activity to a level ideal for infection. This interaction is conserved across the filoviruses and may provide an opportunity for therapeutic development.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
8.8
作者：
Leung DW;Borek D;Luthra P;Binning JM;Anantpadma M;Liu G;Harvey IB;Su Z;Endlich-Frazier A;Pan J;Shabman RS;Chiu W;Davey RA;Otwinowski Z;Basler CF;Amarasinghe GK
通讯作者：
Amarasinghe GK
影响因子：
5
作者：
Groseth, A.;Charton, J. E.;Sauerborn, M.;Feldmann, F.;Jones, S. M.;Hoenen, T.;Feldmann, H.
通讯作者：
Feldmann, H.
影响因子：
3.7
作者：
ELLIOTT, LH;KILEY, MP;MCCORMICK, JB
通讯作者：
MCCORMICK, JB
影响因子：
5.4
作者：
Hoenen, Thomas;Shabman, Reed S.;Feldmann, Heinz
通讯作者：
Feldmann, Heinz