The Ebola Viral Protein 35 N-Terminus Is a Parallel Tetramer
| Autor: | Wenjie Wang, David S. Jordan, Daisy W. Leung, Tom J. Brett, Yanchun Lin, Michael L. Gross, Chao Wu, Chamnongsak Ken Chanthamontri |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
biology Viral protein Chemistry 030302 biochemistry & molecular biology Protein domain RNA Filoviridae Computational biology biology.organism_classification medicine.disease_cause Ebolavirus Biochemistry Article 03 medical and health sciences Tetramer Protein Domains medicine Escherichia coli Viral Regulatory and Accessory Proteins Amino Acid Sequence Protein Multimerization Mononegavirales Peptide sequence Gene |
| Zdroj: | Biochemistry. 58(6) |
| ISSN: | 1520-4995 |
| Popis: | Members of Mononegavirales, the order including non-segmented negative sense RNA viruses (NNSV), encode a small number of multifunctional proteins. In members of the Filoviridae family, virus protein 35 (VP35) facilitates immune evasion and functions as an obligatory co-factor for viral RNA-synthesis. VP35 functions in an orthologous manner to phosphoproteins (P proteins) from other NNSVs. Although the critical roles of Ebola viral VP35 (eVP35) in immune evasion and RNA synthesis are well-appreciated, a complete understanding of its organization its role in carrying out its many functions has yet to be fully realized. In particular, we currently lack information on the role of the oligomerization domain within eVP35. To address this limitation, we report here an investigation of the oligomer structure of eVP35 using hybrid methods that include multi-angle light scattering (MALS), small angle X-ray scattering (SAXS), and crosslinking coupled with mass spectrometry (XL-MS) to determine the shape and orientation of the eVP35 oligomer. Our integrative results are consistent with a parallel tetramer, in which the N-terminal regions that are required for RNA synthesis are all oriented in the same direction. Furthermore, these results define a framework to target the symmetric tetramer for structure-based antiviral discovery. |
| Databáze: | OpenAIRE |
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