Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers

Claudia Blattner; Jeong Hyun Lee; Kwinten Sliepen; Ronald Derking; Emilia Falkowska; Alba Torrents de la Peña; Albert Cupo; Jean-Philippe Julien; Marit van Gils; Peter S. Lee; Wenjie Peng; James C. Paulson; Pascal Poignard; Dennis R. Burton; John P. Moore; Rogier W. Sanders; Ian A. Wilson; Andrew B. Ward

doi:https://doi.org/10.1016/j.immuni.2014.04.008

Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers

Claudia Blattner, Jeong Hyun Lee, Kwinten Sliepen, Ronald Derking, Emilia Falkowska, Alba Torrents de la Peña, Albert Cupo, Jean-Philippe Julien, Marit van Gils, Peter S. Lee, Wenjie Peng, James C. Paulson, Pascal Poignard, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Ian A. Wilson, Andrew B. Ward

Research output: Contribution to journal › Article › Academic › peer-review

278 Citations (Scopus)

Abstract

All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer

Original language	English
Pages (from-to)	669-680
Journal	Immunity
Volume	40
Issue number	5
DOIs	https://doi.org/10.1016/j.immuni.2014.04.008
Publication status	Published - 2014

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https://doi.org/10.1016/j.immuni.2014.04.008

Cite this

Blattner, C., Lee, J. H., Sliepen, K., Derking, R., Falkowska, E., de la Peña, A. T., Cupo, A., Julien, J.-P., van Gils, M., Lee, P. S., Peng, W., Paulson, J. C., Poignard, P., Burton, D. R., Moore, J. P., Sanders, R. W., Wilson, I. A., & Ward, A. B. (2014). Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity, 40(5), 669-680. https://doi.org/10.1016/j.immuni.2014.04.008

@article{ce6d362a491d4ef8823cee094bcba5be,

title = "Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers",

abstract = "All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer",

author = "Claudia Blattner and Lee, {Jeong Hyun} and Kwinten Sliepen and Ronald Derking and Emilia Falkowska and {de la Pe{\~n}a}, {Alba Torrents} and Albert Cupo and Jean-Philippe Julien and {van Gils}, Marit and Lee, {Peter S.} and Wenjie Peng and Paulson, {James C.} and Pascal Poignard and Burton, {Dennis R.} and Moore, {John P.} and Sanders, {Rogier W.} and Wilson, {Ian A.} and Ward, {Andrew B.}",

year = "2014",

doi = "https://doi.org/10.1016/j.immuni.2014.04.008",

language = "English",

volume = "40",

pages = "669--680",

journal = "Immunity",

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Blattner, C, Lee, JH, Sliepen, K, Derking, R, Falkowska, E, de la Peña, AT, Cupo, A, Julien, J-P, van Gils, M, Lee, PS, Peng, W, Paulson, JC, Poignard, P, Burton, DR, Moore, JP, Sanders, RW, Wilson, IA & Ward, AB 2014, 'Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers', Immunity, vol. 40, no. 5, pp. 669-680. https://doi.org/10.1016/j.immuni.2014.04.008

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AU - Blattner, Claudia

AU - Lee, Jeong Hyun

AU - Sliepen, Kwinten

AU - Derking, Ronald

AU - Falkowska, Emilia

AU - de la Peña, Alba Torrents

AU - Cupo, Albert

AU - Julien, Jean-Philippe

AU - van Gils, Marit

AU - Lee, Peter S.

AU - Peng, Wenjie

AU - Paulson, James C.

AU - Poignard, Pascal

AU - Burton, Dennis R.

AU - Moore, John P.

AU - Sanders, Rogier W.

AU - Wilson, Ian A.

AU - Ward, Andrew B.

PY - 2014

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AB - All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer

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DO - https://doi.org/10.1016/j.immuni.2014.04.008

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SN - 1074-7613

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