TY - JOUR
T1 - Three-dimensional structure of HIV-1 virus-like particles by electron cryotomography
AU - Benjamin, Jordan
AU - Ganser-Pornillos, Barbie K.
AU - Tivol, William F.
AU - Sundquist, Wesley I.
AU - Jensen, Grant J.
N1 - Funding Information:
This work was supported by NIH grant PO1 GM66521 to W.I.S. and G.J.J., as well as gifts from the Ralph M. Parsons Foundation, the Agouron Institute, and the Gordon and Betty Moore Foundation to the California Institute of Technology. We are grateful to Uta von Schwedler and Kirsten Stray for assistance with VLP preparations, and we thank Simon Wain–Hobsen for suggesting that we estimate the concentrations of enzymes in the viral core.
PY - 2005/2/18
Y1 - 2005/2/18
N2 - While the structures of nearly every HIV-1 protein are known in atomic detail from X-ray crystallography and NMR spectroscopy, many questions remain about how the individual proteins are arranged in the mature infectious viral particle. Here, we report the three-dimensional structures of individual HIV-1 virus-like particles (VLPs) as obtained by electron cryotomography. These reconstructions revealed that while the structures and positions of the conical cores within each VLP were unique, they exhibited several surprisingly consistent features, including similarities in the size and shape of the wide end of the capsid (the "base"), uniform positioning of the base and other regions of the capsid 11 nm away from the envelope/MA layer, a cone angle that typically varied from 24° to 18° around the long axis of the cone, and an internal density (presumably part of the NC/RNA complex) cupped within the base. Multiple and nested capsids were observed. These results support the fullerene cone model for the viral capsid, indicate that viral maturation involves a free re-organization of the capsid shell rather than a continuous condensation, imply that capsid assembly is both concentration-driven and template-driven, suggest that specific interactions exist between the capsid and the adjacent envelope/MA and NC/RNA layers, and show that a particular capsid shape is favored strongly in-vivo.
AB - While the structures of nearly every HIV-1 protein are known in atomic detail from X-ray crystallography and NMR spectroscopy, many questions remain about how the individual proteins are arranged in the mature infectious viral particle. Here, we report the three-dimensional structures of individual HIV-1 virus-like particles (VLPs) as obtained by electron cryotomography. These reconstructions revealed that while the structures and positions of the conical cores within each VLP were unique, they exhibited several surprisingly consistent features, including similarities in the size and shape of the wide end of the capsid (the "base"), uniform positioning of the base and other regions of the capsid 11 nm away from the envelope/MA layer, a cone angle that typically varied from 24° to 18° around the long axis of the cone, and an internal density (presumably part of the NC/RNA complex) cupped within the base. Multiple and nested capsids were observed. These results support the fullerene cone model for the viral capsid, indicate that viral maturation involves a free re-organization of the capsid shell rather than a continuous condensation, imply that capsid assembly is both concentration-driven and template-driven, suggest that specific interactions exist between the capsid and the adjacent envelope/MA and NC/RNA layers, and show that a particular capsid shape is favored strongly in-vivo.
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U2 - 10.1016/j.jmb.2004.11.064
DO - 10.1016/j.jmb.2004.11.064
M3 - Article
C2 - 15670606
AN - SCOPUS:12544255655
SN - 0022-2836
VL - 346
SP - 577
EP - 588
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 2
ER -
