VP24

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 (3).

Marburg 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).

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(1,5).

(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 stick 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).