Consideration of the three-dimensional structure of core shells (capsids) in spherical retroviruses.
The problem of three-dimensional organization of retroviral cores has been a matter of interest for the past 30 years. The general opinion in favor of icosahedral symmetry based on electron microscopy observations was questioned when cryo-electron microscopy failed to provide convincing evidence in its favor. More recent studies by cryo-electron microscopy, X-ray crystallography and in vitro assembly of the CA domain of Human immuno deficiency virus (HIV), Murine leukemia virus (MuLV) and Rous sarcoma virus (RSV) threw new light on the organization of retroviral cores. In this communication we report how we produced a three-dimensional (3D) model of MuLV core using data from CA assembly on a lipid film [Ganser, B.K., Cheng, A., Sundquist, W.I., Yeager, M., 2003. Three-dimensional structure of the M-MuLV CA protein on a lipid monolayer: a general model for retroviral capsid assembly. EMBO J. 22, 2886-2892]. The resulting structure revealed that the molecular organization of the core shell is specific and the presence of a 5,3,2 rotational symmetry of the 3D model provides support for icosahedral shape of MuLV cores. The model made it possible to determine the diameter of the cores and calculate the number of CA copies as well as the molecular mass of a core of specific diameter. Thus MuLV cores 68 (or 81.6) nm in diameter consist of 1500 (or 2160) copies of CA. About 12% of molecules from fullerene-like Gag shells versus 71% of molecules of closely packed (core-like). Gag shells were not incorporated into the core shells (capsids). Our 3D models received support from X-ray data of MuLV CA NTD domain published by Mortuza et al. [Mortuza, G., Haire, L.F., Stevens, A., Smerdon, S.J., Stoye, J.P., Taylor, I.A., 2004. High resolution structure of a retroviral capsid hexameric amino-terminal domain. Nature 431, 481-485].
Nermut
Milan V
MV
Laboratory for Molecular Structure, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Herts. EN6 3QG, UK. mnermut@nimr.mrc.ac.uk
Mulloy
Barbara
B
D000818:Animals; D002213:Capsid / Q000648:ultrastructure*; D036022:Capsid Proteins / Q000648:ultrastructure; D005612:Freeze Drying; D021621:Imaging, Three-Dimensional; D009052:Leukemia Virus, Murine / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D008954:Models, Biological; D012190:Retroviridae / Q000648:ultrastructure*; D019065:Virus Assembly
D036022:Capsid Proteins