VP24
VP24
IntroductionVP24 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]. FunctionEbola 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 binds to karyopherin 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 CharacteristicsThe 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]. Ebola Domain (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
| ||||||||||||
3D Structures of VP24
Updated on 04-January-2015
