Abstract
The major structural components of HIV-1 are encoded as a single polyprotein, Gag, which is sufficient for virus particle assembly. Initially, Gag forms an approximately spherical shell underlying the membrane of the immature particle. After proteolytic maturation of Gag, the capsid (CA) domain of Gag reforms into a conical shell enclosing the RNA genome. This mature shell contains 1,000–1,500 CA proteins assembled into a hexameric lattice with a spacing of 10 nm. By contrast, little is known about the structure of the immature virus. We used cryo-EM and scanning transmission EM to determine that an average (145 nm diameter) complete immature HIV particle contains ∼5,000 structural (Gag) proteins, more than twice the number from previous estimates. In the immature virus, Gag forms a hexameric lattice with a spacing of 8.0 nm. Thus, less than half of the CA proteins form the mature core.
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Acknowledgements
We thank D.I. Stuart, E.Y. Jones, R. Matadeen, R.L. Kingston and R.J. Hurrelbrink for critical readings of the manuscript, D.I. Stuart and E.Y. Jones for discussions of diffraction analysis and K.V. Fernando for help with programming. The BNL STEM is a US National Institutes of Health (NIH) supported resource center, NIH P41–RR01777, with additional support provided by the US Department of Energy, Office of Biological and Environmental Research. This work was supported by a Wellcome Trust Programme Grant to S.D.F., a US Public Health Service grant to V.M.V. and a Deutsche Forschungsgemeinschaft grant to H.-G.K. J.A.G.B. holds a Wellcome Trust structural biology studentship. S.D.F. is a Wellcome Trust principal research fellow.
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Briggs, J., Simon, M., Gross, I. et al. The stoichiometry of Gag protein in HIV-1. Nat Struct Mol Biol 11, 672–675 (2004). https://doi.org/10.1038/nsmb785
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DOI: https://doi.org/10.1038/nsmb785
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