An all-atom model of the pore-like structure of hexameric VP40 from Ebola: structural insights into the monomer-hexamer transition.
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 30 A. In this paper, we present the refinement of the EM reconstruction of truncated hexameric VP40 to approximately 20 A and the construction of an all-atom model (residues 44-212) using the EM model at approximately 20 A 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.
Nguyen
Tam Luong
TL
Target Structure-Based Drug Discovery Group, Developmental Therapeutics Program, SAIC, National Cancer Institute, Frederick, MD 21702, USA.
Schoehn
Guy
G
Weissenhorn
Winfried
W
Hermone
Ann R
AR
Burnett
James C
JC
Panchal
Rekha G
RG
McGrath
Connor
C
Zaharevitz
Dan W
DW
Aman
M Javad
MJ
Gussio
Rick
R
Bavari
Sina
S
D008854:Microscopy, Electron; D008958:Models, Molecular; D009698:Nucleoproteins / Q000737:chemistry*; D011487:Protein Conformation; D014758:Viral Core Proteins / Q000737:chemistry*; D014961:X-Ray Diffraction
D009698:Nucleoproteins; D014758:Viral Core Proteins; C084819:nucleoprotein VP40, Ebola virus