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

Function

Ebola

In a normal immune response interferons (IFN) are produced to alert surrounding cells to the presence of a pathogen. This response activates STAT1 by phosphorylation. STAT1 is a transcription factor that increases production of immune fighting genes in cells, 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.

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.

Structural Characteristics

The Ebola and Marburg VP24 proteins are 30% identical. 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. Additionally, the N termini of Ebola (Zaire) and the Marburg virus are very similar in function. They are used by the for proper nucleocapsid functioning.

(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. 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."

Unlike the Ebola domain, the Marburg domain has two beta strands present that stick out from the structure. Another difference is that the Marburg VP24 doesn't use an alpha helix to bind to another VP24. Instead, it uses a flexible strand that binds to a groove, not a pocket, found in another VP24.