Zika virus nonstructural protein 5 residue R681 is critical for dimer formation and enzymatic activity
Zika virus (ZIKV) relies on its nonstructural protein 5 (NS5) for capping and synthesis of the viral RNA. Recent small-angle X-ray scattering (SAXS) data of recombinant ZIKV NS5 protein showed that it is dimeric in solution. Here, we present insights into the critical residues responsible for its di...
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| Format: | Journal Article |
| Language: | English |
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2021
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| Online Access: | https://hdl.handle.net/10356/149251 |
| _version_ | 1811690065076682752 |
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| author | Saw, Wuan-Geok Chan, Kitti Wing-Ki Vasudevan, Subhash G. Grüber, Gerhard |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Saw, Wuan-Geok Chan, Kitti Wing-Ki Vasudevan, Subhash G. Grüber, Gerhard |
| author_sort | Saw, Wuan-Geok |
| collection | NTU |
| description | Zika virus (ZIKV) relies on its nonstructural protein 5 (NS5) for capping and synthesis of the viral RNA. Recent small-angle X-ray scattering (SAXS) data of recombinant ZIKV NS5 protein showed that it is dimeric in solution. Here, we present insights into the critical residues responsible for its dimer formation. SAXS studies of the engineered ZIKV NS5 mutants revealed that R681A mutation on NS5 (NS5R681A ) disrupts the dimer formation and affects its RNA-dependent RNA polymerase activity as well as the subcellular localization of NS5R681A in mammalian cells. The critical residues involved in the dimer arrangement of ZIKV NS5 are discussed, and the data provide further insights into the diversity of flaviviral NS5 proteins in terms of their propensity for oligomerization. |
| first_indexed | 2024-10-01T05:58:04Z |
| format | Journal Article |
| id | ntu-10356/149251 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:58:04Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1492512023-02-28T17:10:08Z Zika virus nonstructural protein 5 residue R681 is critical for dimer formation and enzymatic activity Saw, Wuan-Geok Chan, Kitti Wing-Ki Vasudevan, Subhash G. Grüber, Gerhard School of Biological Sciences Science::Biological sciences::Biochemistry Flavivirus Zika Zika virus (ZIKV) relies on its nonstructural protein 5 (NS5) for capping and synthesis of the viral RNA. Recent small-angle X-ray scattering (SAXS) data of recombinant ZIKV NS5 protein showed that it is dimeric in solution. Here, we present insights into the critical residues responsible for its dimer formation. SAXS studies of the engineered ZIKV NS5 mutants revealed that R681A mutation on NS5 (NS5R681A ) disrupts the dimer formation and affects its RNA-dependent RNA polymerase activity as well as the subcellular localization of NS5R681A in mammalian cells. The critical residues involved in the dimer arrangement of ZIKV NS5 are discussed, and the data provide further insights into the diversity of flaviviral NS5 proteins in terms of their propensity for oligomerization. Ministry of Education (MOE) National Medical Research Council (NMRC) Accepted version The research was supported by National Medical Research Council grants NMRC/CBRG/0103/2016 to SGV; National Research Foundation grant NRF2016NRF-CRP001-063 as co-PI to SGV, and Ministry of Health grant MOH-000086 (MOH-OFIRG18may-0006/2019) to SGV and the Ministry of Education MOE Tier 3 grant (MOE2012-T3-1-008) to GG. 2021-05-19T07:06:15Z 2021-05-19T07:06:15Z 2019 Journal Article Saw, W., Chan, K. W., Vasudevan, S. G. & Grüber, G. (2019). Zika virus nonstructural protein 5 residue R681 is critical for dimer formation and enzymatic activity. FEBS Letters, 593(12), 1272-1291. https://dx.doi.org/10.1002/1873-3468.13437 0014-5793 https://hdl.handle.net/10356/149251 10.1002/1873-3468.13437 31090058 2-s2.0-85066470708 12 593 1272 1291 en FEBS Letters © 2019 Federation of European Biochemical Societies (FEBS). All rights reserved. This paper was published in FEBS Letters and is made available with permission of Federation of European Biochemical Societies (FEBS). application/pdf |
| spellingShingle | Science::Biological sciences::Biochemistry Flavivirus Zika Saw, Wuan-Geok Chan, Kitti Wing-Ki Vasudevan, Subhash G. Grüber, Gerhard Zika virus nonstructural protein 5 residue R681 is critical for dimer formation and enzymatic activity |
| title | Zika virus nonstructural protein 5 residue R681 is critical for dimer formation and enzymatic activity |
| title_full | Zika virus nonstructural protein 5 residue R681 is critical for dimer formation and enzymatic activity |
| title_fullStr | Zika virus nonstructural protein 5 residue R681 is critical for dimer formation and enzymatic activity |
| title_full_unstemmed | Zika virus nonstructural protein 5 residue R681 is critical for dimer formation and enzymatic activity |
| title_short | Zika virus nonstructural protein 5 residue R681 is critical for dimer formation and enzymatic activity |
| title_sort | zika virus nonstructural protein 5 residue r681 is critical for dimer formation and enzymatic activity |
| topic | Science::Biological sciences::Biochemistry Flavivirus Zika |
| url | https://hdl.handle.net/10356/149251 |
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