Seattle Structural Genomics Center for Infectious Disease

Ebolavirus VP40

The Ebola virus is the causative agent for Ebola hemorrhagic disease in humans and in other mammals. Since 1976 there have been approximately 35 outbreaks of the Ebola virus with the most recent outbreak infecting more than 24,000 people and causing nearly 10,000 deaths. Although there has been a large effort to develop treatments or vaccines against the Ebola virus, there are currently no known cures for Ebola hemorrhagic disease. Of the five known strains, the Sudan Ebolavirus (SUDV) has caused five different outbreaks including the second largest outbreak between 2000 and 2001. The genome of SUDV is made up of seven genes, including the viral matrix which plays an essential role in virus assembly and packaging. Understanding the specific viral structure of the matrix protein from SUDV will be crucial to learning the mechanism of the disease.


In collaboration with the laboratory of Erica Ollmann Saphire at the Scripps Research Institute in La Jolla, California; the Seattle Structural Genomics Center for Infectious Disease (SSGCID) has determined the high-resolution structure of SUDV VP40 dimer. During the viral lifecycle, VP40 exists in multiple oligomeric states including dimer, hexamer, and an octomer when bound to RNA. In this structure, VP40 is assembled as a dimer which is believed to be the precursor for larger VP40 assemblies. The individual monomer is comprised of two domains that are connected by a flexible linker. The N-terminal domain (blue) creates a seven-stranded β-sandwich and the more disordered C-terminal domain (orange) contains a combination of α helices and β-sheets. During the viral budding process, there is a structural rearrangement of VP40 to create a conserved C-terminal domain packing interaction.  This higher resolution structure shows several previously disordered residues at the C-terminal domain that may play a role in this reorganization.


Details of this work have been accepted to the Journal Acta Crystallographica Section F. Reference: High-resolution crystal structure of dimeric VP40 from Sudan ebolavirus. Clifton, M.C., Bruhn, J.F., Atkins, K., Webb, T., Baydo, R., Raymond, A., Lorimor, D., Edwards, T.E., Myler P.J., Ollmann-Saphire, E. In Press. Coordinates are available in the Protein Data Bank, PDBID 3TCQ