An All-Atom Model of the Pore-Like Structure of Hexameric VP40 from Ebola: Structural Insights into the Monomer-Hexamer Transition
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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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.