Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope glycoproteins display the same closed and open quaternary molecular architectures

Audray Harris, Mario J. Borgnia, Dan Shi, Alberto Bartesaghi, Haifeng He, Robert Pejchal, Yun Kang, Rafael Depetris, Andre J. Marozsan, Rogier W. Sanders, Per Johan Klasse, Jacqueline L S Milne, Ian A. Wilson, William C. Olson, John P. Moore, Sriram Subramaniam

Research output: Contribution to journalArticle

Abstract

The initial step in HIV-1 infection occurs with the binding of cell surface CD4 to trimeric HIV-1 envelope glycoproteins (Env), a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120). The design of soluble versions of trimeric Env that display structural and functional properties similar to those observed on intact viruses is highly desirable from the viewpoint of designing immunogens that could be effective as vaccines against HIV/AIDS. Using cryoelectron tomography combined with subvolume averaging, we have analyzed the structure of SOSIP gp140 trimers, which are cleaved, solubilized versions of the ectodomain of trimeric HIV-1 Env. We show that unliganded gp140 trimers adopt a quaternary arrangement similar to that displayed by native unliganded trimers on the surface of intact HIV-1 virions. When complexed with soluble CD4, Fab 17b, which binds to gp120 at its chemokine coreceptor binding site, or both soluble CD4 and 17b Fab, gp140 trimers display an open conformation in which there is an outward rotation and displacement of each gp120 protomer. We demonstrate that the molecular arrangements of gp120 trimers in the closed and open conformations of the soluble trimer are the same as those observed for the closed and open states, respectively, of trimeric gp120 on intact HIV-1 BaL virions, establishing that soluble gp140 trimers can be designed to mimic the quaternary structural transitions displayed by native trimeric Env.

Original languageEnglish (US)
Pages (from-to)11440-11445
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number28
DOIs
StatePublished - Jul 12 2011
Externally publishedYes

Keywords

  • AIDS vaccine
  • Cryoelectron microscopy
  • HIV spike
  • HIV vaccine
  • Viral entry

ASJC Scopus subject areas

  • General

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  • Cite this

    Harris, A., Borgnia, M. J., Shi, D., Bartesaghi, A., He, H., Pejchal, R., Kang, Y., Depetris, R., Marozsan, A. J., Sanders, R. W., Klasse, P. J., Milne, J. L. S., Wilson, I. A., Olson, W. C., Moore, J. P., & Subramaniam, S. (2011). Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope glycoproteins display the same closed and open quaternary molecular architectures. Proceedings of the National Academy of Sciences of the United States of America, 108(28), 11440-11445. https://doi.org/10.1073/pnas.1101414108