VP24

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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 <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(3). With the karyopherin proteins bound, P-STAT1 does not make it to the nucleus which greatly weakens the immune response in cells (3).
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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 <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. 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>do 10.1016/j.celrep.2014.01.043</ref>.
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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>.
== Structural Characteristics ==
== Structural Characteristics ==
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== References ==
== References ==
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<references/>
 
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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
 
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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
 
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<references/>
<references/>

Revision as of 07:58, 6 November 2014

VP24

VP24 from the Reston Ebola Virus 4d9o

Drag the structure with the mouse to rotate

References

  1. ↑ 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. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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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