VP24: Difference between revisions

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<StructureSection load='4d9o' size='340' side='right' caption='VP24 from the Reston Ebola Virus [[4d9o]]' 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 <ref name='Marburg '>pmid 24574400</ref>.
'''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>.


== Function ==
== Function ==
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'''Ebola'''
'''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 <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).  
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'''


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>.
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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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 '/>.
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 '/>.


== References ==
<references/>
</StructureSection>
</StructureSection>


== References ==
== 3D Structures of VP24 ==
<references/>
 
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
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*VP24 from Sudan ebola
 
**[[3vne]], [[3vnf]] – VP24 (mutant) <BR />
 
*VP24 from Reston ebola
 
**[[4d9o]] – VP24 <BR />
 
*VP24 from Zaire ebola
 
**[[4m0q]] – VP24 <BR />
**[[4u2x]] – VP24 + importin subunit alpha-6<br />
**[[6ehm]] – VP24 + nucleoprotein<BR />
 
*VP24 from Marburg virus
 
**[[4or8]] – VP24 <BR />
 
*VP24 from White spot syndrome virus
 
**[[5hlj]] – VP24 <BR />
 
*VP24 from apple latent spherical virus
 
**[[7chk]] – VP24+VP20+VP25 - Cryo EM<BR />


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
}}


<references/>
[[Category:Topic Page]]

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Wally Novak, Jaime Prilusky, Michal Harel