Читать книгу Principles of Virology - Jane Flint, S. Jane Flint - Страница 183

Diverse lines of evidence support a fullerene cone model of this capsid based on principles that underlie the formation of icosahedral and helical structures.

(A) A purified human immunodeficiency virus type 1 protein comprising the capsid linked to the nucleocapsid proteins, CA-NC self-assembles into cylinders and cones when incubated with a segment of the viral RNA genome in vitro. The cones assembled in vitro are capped at both ends, and many appear very similar in dimensions and morphology to cores isolated from viral particles (compare the two panels, shown at the same scale, as indicated by the bars). From Ganser BK et al. 1999. Science 283:80–83, with permission. Courtesy of W. Sundquist, University of Utah. (B) The very regular appearance of the synthetic CA-NC cones suggested that, despite their asymmetry, they are constructed from a regular, underlying lattice analogous to the lattices that describe structures with icosahedral symmetry discussed in Box 4.3. In fact, the human immunodeficiency virus type 1 cores can be modeled using the geometric principles that describe cones formed from carbon. Such elemental carbon cones comprise helices of hexamers closed at each end by caps of buck-minsterfullerene, which are structures that contain pentamers surrounded by hexamers. As in structures with icosahedral symmetry, the positions of pentamers determine the geometry of cones. However, in cones, pentamers are present only in the terminal caps. The human immunodeficiency virus type 1 cones formed in vitro and isolated from mature virions can be modeled as a fullerene cone assembling on a curved hexagonal lattice with five pentamers (red) at the narrow end of the cone, as shown in the expanded view. The wide end would be closed by an additional 7 pentamers (because 12 pentamers are required to form a closed structure from a hexagonal lattice). (C) The fullerene cone model was subsequently confirmed and refined by cryo-EM of helical tubes of CA at higher resolution, molecular dynamics simulations, and cryo-EM of cores purified from and within virus particles. Shown is an example of computational slices of perfect fullerene cones observed within virus particles, with cryoelectron tomographic models superimposed. The C-terminal domains of CA molecules are shown in gray, the N-terminal domains of CA pentamers in blue, and those of CA hexamers colored according to the quality of their alignment, from red (low) to green (high). From Mattei S. 2017. Science 354:1434–1437, with permission. Courtesy of J. Briggs, European Molecular Biology Laboratory, Heidelberg, Germany.

 Li S, Hill CP, Sundquist WI, Finch JT. 2000. Image reconstructions of helical assemblies of the HIV-1 CA protein. Nature 407:409–413.

 Zhao G, Perilla JR, Yufenyuy EL, Meng X, Chen B, Ning J, Ahn J, Gronenborn AM, Schulten K, Aiken C, Zhang P. 2013. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497:643–646.

 Mattei S, Glass B, Hagen WJH, Kräusslich H-G, Briggs JAG. 2016. The structure and flexibility of conical HIV-1 capsids determined within intact virions. Science 354:1434–1437.