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| | ==VP24== | | ==VP24== |
| - | <StructureSection load='4D9O' size='340' side='right' caption='VP24 from the Reston Ebola Virus' scene=''> | + | <StructureSection load='4d9o' size='340' side='right' caption='VP24 from the Reston Ebola Virus [[4d9o]]' scene=''> |
| | == Introduction == | | == Introduction == |
| - | VP24 is a protein present in the Ebola and Marburg viruses, both of which are members of ''Filoviridae'' family. Presently there are five strains of Ebola: Sudan, Reston, Zaire, Bundibugyo, and Taï Forest, each with minor differences in VP24 sequences(1). | + | '''VP24''' is a protein present in the Ebola and Marburg viruses, both of which are members of ''Filoviridae'' family. Presently there are five strains of Ebola: Sudan, Reston, Zaire, Bundibugyo, and Taï Forest, each with minor differences in VP24 sequences <ref name='Marburg '>pmid 24574400</ref>. |
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| | == Function == | | == Function == |
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| | '''Ebola''' | | '''Ebola''' |
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| - | In a normal immune response interferons (IFN) are produced to alert surrounding cells to the presence of a pathogen, which activates STAT1 by phosphorylation(2). STAT1 is a transcription factor that increases production of immune fighting genes in cells, STAT1 is brought to the nucleus by karyopherin α proteins(2). Ebola protein VP24 <scene name='60/602719/Vp24_bound_to_karyopherin_a5/1'>binds to karyopherin</scene> α1, α5, and α6, which normally bring the P-STAT1 to the nucleus(3). With the karyopherin proteins bound, P-STAT1 does not make it to the nucleus which greatly weakens the immune response in cells (3). | + | In a normal immune response interferons (IFN) are produced to alert surrounding cells to the presence of a pathogen, which activates STAT1 by phosphorylation <ref name='4or8'>pmid 24574400</ref>. STAT1 is a transcription factor that increases production of immune fighting genes in cells, STAT1 is brought to the nucleus by karyopherin α proteins <ref name='4or8'/>. Ebola protein VP24 <scene name='60/602719/Vp24_bound_to_karyopherin_a5/1'>binds to karyopherin</scene> α1, α5, and α6, which normally bring the P-STAT1 to the nucleus <ref>DOI: 10.1016/j.chom.2014.07.008</ref>. With the karyopherin proteins bound, P-STAT1 does not make it to the nucleus which greatly weakens the immune response in cells <ref>DOI: 10.1016/j.chom.2014.07.008</ref>. |
| | '''Marburg''' | | '''Marburg''' |
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| - | Keap1 is a protein that degrades the transcription factor Nrf2(4). VP24 in the Marburg virus targets and binds the Keap1 protein, and as a result leaves Nrf2 unaltered(4). High levels of Nrf2 triggers antioxidant response elements(ARE)(4). This causes cells to become defensive, which protects the Marburg virus inside the cell(4). | + | Keap1 is a protein that degrades the transcription factor Nrf2. VP24 in the Marburg virus targets and binds the Keap1 protein, and as a result leaves Nrf2 unaltered. High levels of Nrf2 triggers antioxidant response elements(ARE). This causes cells to become defensive, which protects the Marburg virus inside the cell <ref>doi 10.1016/j.celrep.2014.01.043</ref>. |
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| | == Structural Characteristics == | | == Structural Characteristics == |
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| - | The Ebola and Marburg VP24 proteins are 30% identical(1). They share a similar pyramidal shaped domain, as well as a few structures. Both viruses have two highly conserved pockets underneath the "pyramid's" base (1). Additionally, the N termini of Ebola (Zaire) and the Marburg virus are very similar in function. They are both used for oligomer and nucleocapsid formation(1,5). | + | The Ebola and Marburg VP24 proteins are 30% identical <ref name='Marburg '/>. They share a similar pyramidal shaped domain, as well as a few structures. Both viruses have two highly conserved pockets underneath the "pyramid's" base <ref name='Marburg '/>. Additionally, the N termini of Ebola (Zaire) and the Marburg virus are very similar in function. They are both used for oligomer and nucleocapsid formation <ref name='Marburg '/><ref>pmid 22371572</ref>. |
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| | <scene name='60/602719/Chain_b/1'>Ebola Domain</scene> (Reston) | | <scene name='60/602719/Chain_b/1'>Ebola Domain</scene> (Reston) |
| - | There are a few structural characteristics only found in the Ebola viruses. At the top of the pyramidal domain, there are α helices present which are thought to interact with the α karyopherin(1). An α helix formed by the N-terminus runs from the top of the "pyramid" to another nearby VP24, where it binds to one of the pockets located underneath the "pyramid"(1). | + | There are a few structural characteristics only found in the Ebola viruses. At the top of the pyramidal domain, there are α helices present which are thought to interact with the α karyopherin <ref name='Marburg '/>. An α helix formed by the N-terminus runs from the top of the "pyramid" to another nearby VP24, where it binds to one of the pockets located underneath the "pyramid" <ref name='Marburg '/>. |
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| | <scene name='60/602719/Marburg_vp24_domain/1'>Marburg Domain</scene> | | <scene name='60/602719/Marburg_vp24_domain/1'>Marburg Domain</scene> |
| - | The Marburg domain has a beta shelf present that sticks out from the structure(1). The Marburg VP24 doesn't use an alpha helix to bind to another VP24 like the Ebola VP24(1). Instead, it uses a flexible strand that binds to a groove of a close-by VP24(1). | + | The Marburg domain has a beta shelf present that sticks out from the structure <ref name='Marburg '/>. The Marburg VP24 doesn't use an alpha helix to bind to another VP24 like the Ebola VP24 <ref name='Marburg '/>. Instead, it uses a flexible strand that binds to a groove of a close-by VP24 <ref name='Marburg '/>. |
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| | + | == References == |
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| | + | <references/> |
| | </StructureSection> | | </StructureSection> |
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| - | == References == | + | == 3D Structures of VP24 == |
| - | 1. Zhang, A.P.P., Bornholdt, Z.A., Abelson, D.M., Saphire, E.O. Crystal Structure of Marburg Virus VP24. J. Virol.2014, Feb 26;88(10):5859
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| - | 2. Zhang, P.P., Abelson, D.M., Bornholdt, Z.A., Liu, T., Woods, V.L. Jr., Saphire, E. O. The ebolavirus VP24 interferon antagonist: Know your enemy. Virulence. 2012, Aug 15;3(5)440-445
| + | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} |
| | + | {{#tree:id=OrganizedByTopic|openlevels=0| |
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| - | 3. Xu, W., Edwards, M.R., Borek, D.M., Feagins, A.R., Mittal, A., Alinger, J.B., Berry, K.N., Yen, B., Hamilton, J., Brett, T.J., Pappu, R.V., Leung, D.W., Basler, C.F., Amarasinghe, G.K. Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1. Cell Host & Microbe. 2014, Aug 13;16 187-200
| + | *VP24 from Sudan ebola |
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| - | 4. Edwards, R. M., Johnson, B., Mire, C.E., Xu, W., Shabman, R.S., Speller, L.N., Leung, D.W., Geisbert, T.W., Amarasinghe, G.K., Basler, C.F. The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway. Cell. 2014, Mar 27. 6 1017-1025
| + | **[[3vne]], [[3vnf]] – VP24 (mutant) <BR /> |
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| - | 5. Bharat, T.A.M., Noda, T., Riches, J.D., Kraehling, V., Kolesnikova, L., Becker, S., Kawaoka, Y., Briggs, J.A.G. Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography. PNAS. 2012, Feb 6 109(11) 4275-4280.
| + | *VP24 from Reston ebola |
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| - | <references/> | + | **[[4d9o]] – VP24 <BR /> |
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| | + | *VP24 from Zaire ebola |
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| | + | **[[4m0q]] – VP24 <BR /> |
| | + | **[[4u2x]] – VP24 + importin subunit alpha-6<br /> |
| | + | **[[6ehm]] – VP24 + nucleoprotein<BR /> |
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| | + | *VP24 from Marburg virus |
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| | + | **[[4or8]] – VP24 <BR /> |
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| | + | *VP24 from White spot syndrome virus |
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| | + | **[[5hlj]] – VP24 <BR /> |
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| | + | *VP24 from apple latent spherical virus |
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| | + | **[[7chk]] – VP24+VP20+VP25 - Cryo EM<BR /> |
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| | + | }} |
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| | + | [[Category:Topic Page]] |
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Introduction
VP24 is a protein present in the Ebola and Marburg viruses, both of which are members of Filoviridae family. Presently there are five strains of Ebola: Sudan, Reston, Zaire, Bundibugyo, and Taï Forest, each with minor differences in VP24 sequences [1].
Function
Ebola
In a normal immune response interferons (IFN) are produced to alert surrounding cells to the presence of a pathogen, which activates STAT1 by phosphorylation [2]. STAT1 is a transcription factor that increases production of immune fighting genes in cells, STAT1 is brought to the nucleus by karyopherin α proteins [2]. Ebola protein VP24 α1, α5, and α6, which normally bring the P-STAT1 to the nucleus [3]. With the karyopherin proteins bound, P-STAT1 does not make it to the nucleus which greatly weakens the immune response in cells [4].
Marburg
Keap1 is a protein that degrades the transcription factor Nrf2. VP24 in the Marburg virus targets and binds the Keap1 protein, and as a result leaves Nrf2 unaltered. High levels of Nrf2 triggers antioxidant response elements(ARE). This causes cells to become defensive, which protects the Marburg virus inside the cell [5].
Structural Characteristics
The Ebola and Marburg VP24 proteins are 30% identical [1]. They share a similar pyramidal shaped domain, as well as a few structures. Both viruses have two highly conserved pockets underneath the "pyramid's" base [1]. Additionally, the N termini of Ebola (Zaire) and the Marburg virus are very similar in function. They are both used for oligomer and nucleocapsid formation [1][6].
(Reston)
There are a few structural characteristics only found in the Ebola viruses. At the top of the pyramidal domain, there are α helices present which are thought to interact with the α karyopherin [1]. An α helix formed by the N-terminus runs from the top of the "pyramid" to another nearby VP24, where it binds to one of the pockets located underneath the "pyramid" [1].
The Marburg domain has a beta shelf present that sticks out from the structure [1]. The Marburg VP24 doesn't use an alpha helix to bind to another VP24 like the Ebola VP24 [1]. Instead, it uses a flexible strand that binds to a groove of a close-by VP24 [1].
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Zhang AP, Bornholdt ZA, Abelson DM, Saphire EO. Crystal Structure of Marburg Virus VP24. J Virol. 2014 May;88(10):5859-63. doi: 10.1128/JVI.03565-13. Epub 2014 Feb 26. PMID:24574400 doi:http://dx.doi.org/10.1128/JVI.03565-13
- ↑ 2.0 2.1 Zhang AP, Bornholdt ZA, Abelson DM, Saphire EO. Crystal Structure of Marburg Virus VP24. J Virol. 2014 May;88(10):5859-63. doi: 10.1128/JVI.03565-13. Epub 2014 Feb 26. PMID:24574400 doi:http://dx.doi.org/10.1128/JVI.03565-13
- ↑ Xu W, Edwards MR, Borek DM, Feagins AR, Mittal A, Alinger JB, Berry KN, Yen B, Hamilton J, Brett TJ, Pappu RV, Leung DW, Basler CF, Amarasinghe GK. Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1. Cell Host Microbe. 2014 Aug 13;16(2):187-200. doi: 10.1016/j.chom.2014.07.008. PMID:25121748 doi:http://dx.doi.org/10.1016/j.chom.2014.07.008
- ↑ Xu W, Edwards MR, Borek DM, Feagins AR, Mittal A, Alinger JB, Berry KN, Yen B, Hamilton J, Brett TJ, Pappu RV, Leung DW, Basler CF, Amarasinghe GK. Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1. Cell Host Microbe. 2014 Aug 13;16(2):187-200. doi: 10.1016/j.chom.2014.07.008. PMID:25121748 doi:http://dx.doi.org/10.1016/j.chom.2014.07.008
- ↑ Edwards MR, Johnson B, Mire CE, Xu W, Shabman RS, Speller LN, Leung DW, Geisbert TW, Amarasinghe GK, Basler CF. The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway. Cell Rep. 2014 Mar 27;6(6):1017-25. doi: 10.1016/j.celrep.2014.01.043. Epub 2014 , Mar 13. PMID:24630991 doi:http://dx.doi.org/10.1016/j.celrep.2014.01.043
- ↑ Bharat TA, Noda T, Riches JD, Kraehling V, Kolesnikova L, Becker S, Kawaoka Y, Briggs JA. Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography. Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4275-80. doi:, 10.1073/pnas.1120453109. Epub 2012 Feb 27. PMID:22371572 doi:http://dx.doi.org/10.1073/pnas.1120453109
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