Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction

Viruses
Nikéa PittmanMavis Agbandje-McKenna

Abstract

LuIII, a protoparvovirus pathogenic to rodents, replicates in human mitotic cells, making it applicable for use to kill cancer cells. This virus group includes H-1 parvovirus (H-1PV) and minute virus of mice (MVM). However, LuIII displays enhanced oncolysis compared to H-1PV and MVM, a phenotype mapped to the major capsid viral protein 2 (VP2). This suggests that within LuIII VP2 are determinants for improved tumor lysis. To investigate this, the structure of the LuIII virus-like-particle was determined using single particle cryo-electron microscopy and image reconstruction to 3.17 Å resolution, and compared to the H-1PV and MVM structures. The LuIII VP2 structure, ordered from residue 37 to 587 (C-terminal), had the conserved VP topology and capsid morphology previously reported for other protoparvoviruses. This includes a core β-barrel and α-helix A, a depression at the icosahedral 2-fold and surrounding the 5-fold axes, and a single protrusion at the 3-fold axes. Comparative analysis identified surface loop differences among LuIII, H-1PV, and MVM at or close to the capsid 2- and 5-fold symmetry axes, and the shoulder of the 3-fold protrusions. The 2-fold differences cluster near the previously identified MVM sialic acid rece...Continue Reading

References

Apr 25, 1977·Journal of Molecular Biology·P TattersallD C Ward
Jan 1, 1987·Advances in Virus Research·S F Cotmore, P Tattersall
Sep 20, 1993·Journal of Molecular Biology·H Wu, M G Rossmann
Nov 13, 2001·Developmental Cell·Z ZádoriP Tijssen
Feb 6, 2002·Journal of Molecular Biology·Alan A SimpsonMichael G Rossmann
Oct 29, 2003·Journal of Virology·Lakshmanan GovindasamyMavis Agbandje-McKenna
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jul 1, 1996·Acta Crystallographica. Section D, Biological Crystallography·G J Kleywegt, T A Jones
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·E Krissinel, K Henrick
Jul 25, 2006·Journal of Structural Biology·Guang TangSteven J Ludtke
Oct 13, 2006·Journal of Structural Biology·Xiaodong YanTimothy S Baker
Nov 23, 2006·Journal of Structural Biology·Chuan Xiao, Michael G Rossmann
Apr 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Susan HafensteinMichael G Rossmann
Mar 28, 2008·Journal of Virology·Nina DiPrimioR Jude Samulski
Nov 5, 2008·Nucleic Acids Research·Mauricio Carrillo-TrippVijay S Reddy
Jan 10, 2009·Nature Protocols·Lorenza BordoliTorsten Schwede
Mar 27, 2009·Journal of Virology·Susan HafensteinMichael G Rossmann
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 10, 2010·Cytokine & Growth Factor Reviews·Jean RommelaereZahari Raykov
May 4, 2012·Journal of Virology·Justin C PaglinoAnthony N van den Pol
Jul 12, 2012·Nature Biotechnology·Stephen J RussellJohn C Bell

❮ Previous
Next ❯

Citations

Apr 24, 2019·Viruses·Mario MietzschMavis Agbandje-McKenna

❮ Previous
Next ❯

Datasets Mentioned

BETA
EMD-7071

Methods Mentioned

BETA
electrophoresis
transmission electron microscopy

Software Mentioned

MAPMAN
PDBeFOLD
VIPERdb
Phenix
MotionCor2
AUTOPP
Molprobity
RIVEM
SSM
AUTO3DEM

Related Concepts