An All-Atom Model of the Pore-Like Structure of Hexameric VP40 from Ebola: Structural Insights into the Monomer-Hexamer Transition
Abstract
The matrix protein VP40 is an indispensable component of viral assembly and budding by the Ebola virus. VP40 is a monomer in solution, but can fold into hexameric and octameric states, two oligomeric conformations that play central roles in the Ebola viral life cycle. While the X-ray structures of monomeric and octameric VP40 have been determined, the structure of hexameric VP40 has only been solved by three-dimensional electron microscopy (EM) to a resolution of approximately 30A. In this paper, we present the refinement of the EM reconstruction of truncated hexameric VP40 to approximately 20A and the construction of an all-atom model (residues 44-212) using the EM model at approximately 20A and the X-ray structure of monomeric VP40 as templates. The hexamer model suggests that the monomer-hexamer transition involves a conformational change in the N-terminal domain that is not evident during octamerization and therefore, may provide the basis for elucidating the biological function of VP40.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 30, 2005
- Accession Number
- ADA467875
Entities
People
- Ann R. Hermone
- Connor Mcgrath
- Dan W. Zaharevitz
- Guy Schoehn
- James C. Burnett
- M. J. Aman
- Rekha G. Panchal
- Rick Gussio
- Sina Bavari
- Tam L. Nguyen
- Winfried Weissenhorn
Organizations
- National Cancer Institute