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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, Zire, Bundibugyo, and Taï Forest, each with minor differences in VP24 sequences(3). The marburg virus has only one strain.  
'''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 ==
'''Ebola'''
'''Ebola'''


In a normal immune response interferons (IFN) are produced to alert surrounding cells of the presence of a pathogen. This response activates STAT1, which increases production of immune fighting genes in cells, by phosphorylation. STAT1 is brought to the nucleus by karyopherin α proteins. Ebola protein VP24 binds to karyopherin α1, α5, and α6, making it unable to transport the P-STAT1 to the nucleus. As a result the immune response in cells is then greatly weakened. The Reston strain is not immuno_____, unlike the other four.
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>doi 10.1016/j.celrep.2014.01.043</ref>.


== Structural Characteristics ==
== Structural Characteristics ==


The ebola and marburg versions are 30% identical.
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>.
 
<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 <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 '/>.
 
<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 <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>
 
== 3D Structures of VP24 ==


<scene name='60/602719/Reston_vp24/1'>Ebola Structure</scene> (Reston)
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
VP24 is crucial for proper functioni of the viral nucleoprotein
{{#tree:id=OrganizedByTopic|openlevels=0|


<scene name='60/602719/Marburg_vp24/1'>Marburg Structure</scene>
*VP24 from Sudan ebola


**[[3vne]], [[3vnf]] – VP24 (mutant) <BR />


<scene name='60/602719/Vp24_chain_a_from_reston_virus/1'>Chain A</scene>
*VP24 from Reston ebola


<scene name='60/602719/Chain_b/1'>Chain B</scene>
**[[4d9o]] – VP24 <BR />


<scene name='60/602719/Vp24_bound_to_karyopherin_a5/1'> VP24 bound to karyopherin α5 </scene>
*VP24 from Zaire ebola
</StructureSection>
 
== References ==
**[[4m0q]] – VP24 <BR />
<references/>
**[[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 />
 
}}
 
[[Category:Topic Page]]

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Wally Novak, Jaime Prilusky, Michal Harel