Abstract
Using an inhibitory synthetic peptide (DP-178) from HIV-1 gp41, we have trapped HIV-1 envelope glycoprotein (Env) undergoing conformational changes during virus entry. Our data show that DP-178 binds gp41 and inhibits Env-mediated membrane fusion after gp120 interacts with cellular receptors, indicating that conformational changes involving the coiled coil domain of gp41 are required for entry. Capture of this fusion-active conformation of Env provides insights into the early events leading to Env-mediated membrane fusion.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hernandez, L., Hoffman, L., Wolfsberg, T. & White, J. Ann. Rev. Cell Dev. Biol. 12, 627–661 (1996).
Moore, J.P., Jameson, B.A., Weiss, R.A. & Sattentau, Q.J. in Viral Fusion Mechanisms (ed. Bentz, J.) 233–289 (CRC Press, Boca Raton, Florida, 1993).
Wain-Hobson, S. Nature 384, 117–118 (1996).
Dimitrov, D.S. Cell 91, 721–730 (1997).
Chan, D.C., Fass, D., Berger, J.M. & Kim, P.S. Cell 89, 263–273 (1997).
Weissenhorn, W., Dessen, A., Harrison, S.C., Skehel, J.J. & Wiley, D.C. Nature 387, 426–430 (1997).
Tan, K., Liu, J. & Lu, M. Proc. Natl. Acad. Sci. USA 94, 12303 (1997).
Wild, C., Oas, T., McDanal, C., Bolognesi, D. & Matthews, T. Proc. Natl. Acad. Sci. USA 89, 10537–10541 (1992).
Wild, C., Greenwell, T. & Matthews, T. AIDS Res. Hum. Retroviruses 9, 1051–1053 (1993).
Wild, C.T., Shugars, D.C., Greenwell, T.K., McDanal, C.B. & Matthews, T.J. Proc. Natl. Acad. Sci. USA 91, 9770–9774 (1994).
Judice, J.K. et al. Proc. Natl. Acad Sci. USA 94, 13426–13430 (1997).
Matthews, T.J., Wild, C., Chen, C.-H., Bolognesi, D.P. & Greenberg, M.L. Immunological Reviews 140, 93–104 (1994).
Lu, M., Blacklow, S.C. & Kim, P.S. Nature Struct. Biol. 2, 1075–1082 (1995).
Wild, C., Greenwell, T., Shugars, D., Rimksy-Clark, L. & Matthews, T. AIDS Res. Hum. Retroviruses 11, 323–325 (1995).
Weiss, C.D. et al. AIDS 10, 241–246 (1996).
Berger, E. AIDS 11, S3–S16 (1997).
Chen, C.-H., Matthews, T.J., McDanal, C.B., Bolognesi, D.P. & Greenberg, M.L. J. Virol. 69, 3771–3777 (1995).
Rimsky, L.T., Shugars, D.C. & Matthews, T.J. J. Virol. 72, 986–993 (1998).
Carr, C.M. & Kim, P.S. Cell 73, 823–832 (1993).
Chambers, P., Pringle, C.R. & Easton, A.J. J. Gen. Virol. 71, 3075–3080 (1990).
Rapaport, D., Ovadia, M. & Shai, Y. EMBO J 14, 5524–5531 (1995).
Lambert, D.M. et al. Proc. Natl. Acad. Sci. USA 93, 2186–2191 (1996).
Yao, Q. & Compans, R.W. Virology 223, 103–112 (1996).
Lombardi, S. et al. Virology 220, 274–284 (1996).
Deng, H.K. et al. Nature 381, 661–666 (1996).
Abacioglu, Y. et al. AIDS Res. Hum. Retroviruses 10, 371–381 (1994).
Montefiori, D.C., Robinson, W.E., Jr., Schuffman, S.S. & Mitchell, W.M. Clin. Microbiol. 26, 231–235 (1988).
Munoz-Barroso, I., Stewart, D., Sakaguchi, K., Appella, E. and Blumenthal, R. J. Cell Biol. 140, 315–323 (1998).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Furuta, R., Wild, C., Weng, Y. et al. Capture of an early fusion-active conformation of HIV-1 gp41. Nat Struct Mol Biol 5, 276–279 (1998). https://doi.org/10.1038/nsb0498-276
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/nsb0498-276
This article is cited by
-
Altered Env conformational dynamics as a mechanism of resistance to peptide-triazole HIV-1 inactivators
Retrovirology (2021)
-
Structure, membrane topology and influence of cholesterol of the membrane proximal region: transmembrane helical anchor sequence of gp41 from HIV
Scientific Reports (2020)
-
Evaluation of the contribution of the transmembrane region to the ectodomain conformation of the human immunodeficiency virus (HIV-1) envelope glycoprotein
Virology Journal (2017)
-
The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions
Nature Communications (2017)
-
Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding
Journal of Biomolecular NMR (2015)