Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers

被引：286

作者：

Blattner, Claudia ^{[1
,2
]}

Lee, Jeong Hyun ^{[1
,2
,3
]}

Sliepen, Kwinten ^{[4
]}

Derking, Ronald ^{[4
]}

Falkowska, Emilia ^{[2
,5
]}

de la Pena, Alba Torrents ^{[4
]}

Cupo, Albert ^{[6
]}

Julien, Jean-Philippe ^{[1
,2
,3
]}

van Gils, Marit ^{[4
]}

Lee, Peter S. ^{[1
]}

Peng, Wenjie ^{[7
,8
]}

Paulson, James C. ^{[7
,8
]}

Poignard, Pascal ^{[2
,5
]}

Burton, Dennis R. ^{[2
,3
,5
,9
,10
]}

Moore, John P. ^{[6
]}

Sanders, Rogier W. ^{[4
,6
]}

Wilson, Ian A. ^{[1
,2
,3
,11
]}

Ward, Andrew B. ^{[1
,2
,3
]}

机构：

[1] Scripps Res Inst, Dept Integrat Struct & Computat Biol Scrip, La Jolla, CA 92037 USA

[2] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[4] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[5] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[6] Cornell Univ, Weill Med Coll, New York, NY 10021 USA

[7] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA

[8] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[9] MIT, Ragon Inst MGH, Cambridge, MA 02129 USA

[10] Harvard, Cambridge, MA 02129 USA

[11] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

IMMUNITY | 2014年 / 40卷 / 05期

基金：

加拿大自然科学与工程研究理事会; 加拿大健康研究院; 欧洲研究理事会;

关键词：

BROADLY NEUTRALIZING ANTIBODIES; POTENT NEUTRALIZATION; RECOGNITION; IDENTIFICATION; COMBINATION; REFINEMENT; BINDING; SITE; GP41;

D O I：

10.1016/j.immuni.2014.04.008

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：669 / 680

页数：12

共 51 条

[11] HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice [J].

Horwitz, Joshua A. ;

Halper-Stromberg, Ariel ;

Mouquet, Hugo ;

Gitlin, Alexander D. ;

Tretiakova, Anna ;

Eisenreich, Thomas R. ;

Malbec, Marine ;

Gravemann, Sophia ;

Billerbeck, Eva ;

Dorner, Marcus ;

Buening, Hildegard ;

Schwartz, Olivier ;

Knops, Elena ;

Kaiser, Rolf ;

Seaman, Michael S. ;

Wilson, James M. ;

Rice, Charles M. ;

Ploss, Alexander ;

Bjorkman, Pamela J. ;

Klein, Florian ;

Nussenzweig, Michel C. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (41) :16538-16543

[12] Broad and potent neutralization of HIV-1 by a gp41-specific human antibody [J].

Huang, Jinghe ;

Ofek, Gilad ;

Laub, Leo ;

Louder, Mark K. ;

Doria-Rose, Nicole A. ;

Longo, Nancy S. ;

Imamichi, Hiromi ;

Bailer, Robert T. ;

Chakrabarti, Bimal ;

Sharma, Shailendra K. ;

Alam, S. Munir ;

Wang, Tao ;

Yang, Yongping ;

Zhang, Baoshan ;

Migueles, Stephen A. ;

Wyatt, Richard ;

Haynes, Barton F. ;

Kwong, Peter D. ;

Mascola, John R. ;

Connors, Mark .

NATURE, 2012, 491 (7424) :406-+

[13] Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer [J].

Julien, Jean-Philippe ;

Cupo, Albert ;

Sok, Devin ;

Stanfield, Robyn L. ;

Lyumkis, Dmitry ;

Deller, Marc C. ;

Klasse, Per-Johan ;

Burton, Dennis R. ;

Sanders, Rogier W. ;

Moore, John P. ;

Ward, Andrew B. ;

Wilson, Ian A. .

SCIENCE, 2013, 342 (6165) :1477-1483

[14] Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans [J].

Julien, Jean-Philippe ;

Sok, Devin ;

Khayat, Reza ;

Lee, Jeong Hyun ;

Doores, Katie J. ;

Walker, Laura M. ;

Ramos, Alejandra ;

Diwanji, Devan C. ;

Pejchal, Robert ;

Cupo, Albert ;

Katpally, Umesh ;

Depetris, Rafael S. ;

Stanfield, Robyn L. ;

McBride, Ryan ;

Marozsan, Andre J. ;

Paulson, James C. ;

Sanders, Rogier W. ;

Moore, John P. ;

Burton, Dennis R. ;

Poignard, Pascal ;

Ward, Andrew B. ;

Wilson, Ian A. .

PLOS PATHOGENS, 2013, 9 (05)

[15] Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9 [J].

Julien, Jean-Philippe ;

Lee, Jeong Hyun ;

Cupo, Albert ;

Murin, Charles D. ;

Derking, Ronald ;

Hoffenberg, Simon ;

Caulfield, Michael J. ;

King, C. Richter ;

Marozsan, Andre J. ;

Klasse, Per Johan ;

Sanders, Rogier W. ;

Moore, John P. ;

Wilson, Ian A. ;

Ward, Andrew B. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (11) :4351-4356

[16] Structural Characterization of Cleaved, Soluble HIV-1 Envelope Glycoprotein Trimers [J].

Khayat, Reza ;

Lee, Jeong Hyun ;

Julien, Jean-Philippe ;

Cupo, Albert ;

Klasse, Per Johan ;

Sanders, Rogier W. ;

Moore, John P. ;

Wilson, Ian A. ;

Ward, Andrew B. .

JOURNAL OF VIROLOGY, 2013, 87 (17) :9865-9872

[17] Antibodies in HIV-1 Vaccine Development and Therapy [J].

Klein, Florian ;

Mouquet, Hugo ;

Dosenovic, Pia ;

Scheid, Johannes F. ;

Scharf, Louise ;

Nussenzweig, Michel C. .

SCIENCE, 2013, 341 (6151) :1199-1204

[18] HIV therapy by a combination of broadly neutralizing antibodies in humanized mice [J].

Klein, Florian ;

Halper-Stromberg, Ariel ;

Horwitz, Joshua A. ;

Gruell, Henning ;

Scheid, Johannes F. ;

Bournazos, Stylianos ;

Mouquet, Hugo ;

Spatz, Linda A. ;

Diskin, Ron ;

Abadir, Alexander ;

Zang, Trinity ;

Dorner, Marcus ;

Billerbeck, Eva ;

Labitt, Rachael N. ;

Gaebler, Christian ;

Marcovecchio, Paola M. ;

Incesu, Reha-Baris ;

Eisenreich, Thomas R. ;

Bieniasz, Paul D. ;

Seaman, Michael S. ;

Bjorkman, Pamela J. ;

Ravetch, Jeffrey V. ;

Ploss, Alexander ;

Nussenzweig, Michel C. .

NATURE, 2012, 492 (7427) :118-+

[19] Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein [J].

Klein, Florian ;

Gaebler, Christian ;

Mouquet, Hugo ;

Sather, D. Noah ;

Lehmann, Clara ;

Scheid, Johannes F. ;

Kraft, Zane ;

Liu, Yan ;

Pietzsch, John ;

Hurley, Arlene ;

Poignard, Pascal ;

Feizi, Ten ;

Morris, Lynn ;

Walker, Bruce D. ;

Faetkenheuer, Gerd ;

Seaman, Michael S. ;

Stamatatos, Leonidas ;

Nussenzweig, Michel C. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2012, 209 (08) :1469-1479

[20] Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120 [J].

Kong, Leopold ;

Lee, Jeong Hyun ;

Doores, Katie J. ;

Murin, Charles D. ;

Julien, Jean-Philippe ;

McBride, Ryan ;

Liu, Yan ;

Marozsan, Andre ;

Cupo, Albert ;

Klasse, Per-Johan ;

Hoffenberg, Simon ;

Caulfield, Michael ;

King, C. Richter ;

Hua, Yuanzi ;

Le, Khoa M. ;

Khayat, Reza ;

Deller, Marc C. ;

Clayton, Thomas ;

Tien, Henry ;

Feizi, Ten ;

Sanders, Rogier W. ;

Paulson, James C. ;

Moore, John P. ;

Stanfield, Robyn L. ;

Burton, Dennis R. ;

Ward, Andrew B. ;

Wilson, Ian A. .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2013, 20 (07) :796-+

← 1 2 3 4 5 6 →