DOI: 10.1073/pnas.1101414108. Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope glycoproteins display the same closed and open quaternary molecular architectures

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

10.1073/pnas.1101414108

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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.

Bibliography

Harris, A., Borgnia, M. J., Shi, D., Bartesaghi, A., He, H., Pejchal, R., Kang, Y. (Kenneth), 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, 108(28), 11440â11445.

Authors 16

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

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P Klasse, R Sanders, A Cerutti, J Moore, How can HIV-type-1 Env immunogenicity be improved to facilitate antibody-based vaccine development? AIDS Res Hum Retroviruses, 10.1089/aid.2011.0053. (2011). / AIDS Res Hum Retroviruses / How can HIV-type-1 Env immunogenicity be improved to facilitate antibody-based vaccine development? by Klasse P (2011)
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Dates

Type	When
Created	14 years, 2 months ago (June 28, 2011, 5:22 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 7:29 p.m.)
Indexed	2 months, 1 week ago (June 24, 2025, 9:26 a.m.)
Issued	14 years, 2 months ago (June 27, 2011)
Published	14 years, 2 months ago (June 27, 2011)
Published Online	14 years, 2 months ago (June 27, 2011)
Published Print	14 years, 1 month ago (July 12, 2011)

Funders 0

None

BibTeX

@article{Harris_2011, title={Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope glycoproteins display the same closed and open quaternary molecular architectures}, volume={108}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1101414108}, DOI={10.1073/pnas.1101414108}, number={28}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Harris, Audray and Borgnia, Mario J. and Shi, Dan and Bartesaghi, Alberto and He, Haifeng and Pejchal, Robert and Kang, Yun (Kenneth) and Depetris, Rafael and Marozsan, Andre J. and Sanders, Rogier W. and Klasse, Per Johan and Milne, Jacqueline L. S. and Wilson, Ian A. and Olson, William C. and Moore, John P. and Subramaniam, Sriram}, year={2011}, month=jun, pages={11440–11445} }

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