Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer

Sarkar, Anita; Bale, Shridhar; Behrens, Anna-Janina; Kumar, Sonu; Sharma, Shailendra Kumar; de Val, Natalia; Pallesen, Jesper; Irimia, Adriana; Diwanji, Devan C.; Stanfield, Robyn L.; Ward, Andrew B.; Crispin, Max; Wyatt, Richard T.; Wilson, Ian A.

doi:10.1038/s41467-018-04272-y

Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer

Journal Article · Wed May 16 00:00:00 EDT 2018 · Nature Communications

DOI:https://doi.org/10.1038/s41467-018-04272-y· OSTI ID:1502220

^[1]; Bale, Shridhar ^[1]; Behrens, Anna-Janina ^[2]; ^[1]; Sharma, Shailendra Kumar ^[1]; de Val, Natalia ^[1]; Pallesen, Jesper ^[1]; Irimia, Adriana ^[1]; Diwanji, Devan C. ^[1]; Stanfield, Robyn L. ^[1]; Ward, Andrew B. ^[1]; Crispin, Max ^[3]; Wyatt, Richard T. ^[1]; ^[1]

The Scripps Research Inst., La Jolla, CA (United States)
Univ. of Oxford (United Kingdom)
The Scripps Research Inst., La Jolla, CA (United States); Univ. of Oxford (United Kingdom); Univ. of Southampton (United Kingdom)

Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a “closed-form”, native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively. Quantitative site-specific analysis of the glycan shield reveals that native-like glycan processing is maintained despite furin-independent maturation in the secretory pathway. Thus, cleavage-independent NFL Env trimers exhibit quaternary protein and carbohydrate structures similar to the native viral spike that further validate their potential as vaccine immunogen candidates.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Bill & Melinda Gates Foundation; Collaboration for AIDS Vaccine Discovery; Corpus Christi College; International AIDS Vaccine Initiative Neutralizing Antibody Center; National Cancer Institute (NCI); National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID); US Agency for International Development (USAID); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1502220

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 9; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (94)

GLYCAM06: A generalizable biomolecular force field. Carbohydrates: GLYCAM06 Kirschner, Karl N.; Yongye, Austin B.; Tschampel, Sarah M. Journal of Computational Chemistry, Vol. 29, Issue 4 https://doi.org/10.1002/jcc.20820	journal	September 2007
Comparison of multiple Amber force fields and development of improved protein backbone parameters Hornak, Viktor; Abel, Robert; Okur, Asim Proteins: Structure, Function, and Bioinformatics, Vol. 65, Issue 3 https://doi.org/10.1002/prot.21123	journal	November 2006
Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus McCune, Joseph M.; Rabin, Linda B.; Feinberg, Mark B. Cell, Vol. 53, Issue 1 https://doi.org/10.1016/0092-8674(88)90487-4	journal	April 1988
Structural Evolution of Glycan Recognition by a Family of Potent HIV Antibodies Garces, Fernando; Sok, Devin; Kong, Leopold Cell, Vol. 159, Issue 1 https://doi.org/10.1016/j.cell.2014.09.009	journal	September 2014
Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G Stewart-Jones, Guillaume B. E.; Soto, Cinque; Lemmin, Thomas Cell, Vol. 165, Issue 4 https://doi.org/10.1016/j.cell.2016.04.010	journal	May 2016
Cleavage-Independent HIV-1 Env Trimers Engineered as Soluble Native Spike Mimetics for Vaccine Design Sharma, Shailendra Kumar; de Val, Natalia; Bale, Shridhar Cell Reports, Vol. 11, Issue 4 https://doi.org/10.1016/j.celrep.2015.03.047	journal	April 2015
Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers Pritchard, Laura K.; Vasiljevic, Snezana; Ozorowski, Gabriel Cell Reports, Vol. 11, Issue 10 https://doi.org/10.1016/j.celrep.2015.05.017	journal	June 2015
Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies Zhou, Tongqing; Zhu, Jiang; Wu, Xueling Immunity, Vol. 39, Issue 2 https://doi.org/10.1016/j.immuni.2013.04.012	journal	August 2013
A Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans Sok, Devin; Pauthner, Matthias; Briney, Bryan Immunity, Vol. 45, Issue 1 https://doi.org/10.1016/j.immuni.2016.06.026	journal	July 2016
Antibody Elbow Angles are Influenced by their Light Chain Class Stanfield, Robyn L.; Zemla, Adam; Wilson, Ian A. Journal of Molecular Biology, Vol. 357, Issue 5 https://doi.org/10.1016/j.jmb.2006.01.023	journal	April 2006
HIV-1 Envelope Glycoprotein Biosynthesis, Trafficking, and Incorporation Checkley, Mary Ann; Luttge, Benjamin G.; Freed, Eric O. Journal of Molecular Biology, Vol. 410, Issue 4 https://doi.org/10.1016/j.jmb.2011.04.042	journal	July 2011
Topology representing network enables highly accurate classification of protein images taken by cryo electron-microscope without masking Ogura, Toshihiko; Iwasaki, Kenji; Sato, Chikara Journal of Structural Biology, Vol. 143, Issue 3 https://doi.org/10.1016/j.jsb.2003.08.005	journal	September 2003
Automated molecular microscopy: The new Leginon system Suloway, Christian; Pulokas, James; Fellmann, Denis Journal of Structural Biology, Vol. 151, Issue 1 https://doi.org/10.1016/j.jsb.2005.03.010	journal	July 2005
Appion: An integrated, database-driven pipeline to facilitate EM image processing Lander, Gabriel C.; Stagg, Scott M.; Voss, Neil R. Journal of Structural Biology, Vol. 166, Issue 1 https://doi.org/10.1016/j.jsb.2009.01.002	journal	April 2009
A Toolbox for ab initio 3-D reconstructions in single-particle electron microscopy Voss, Neil R.; Lyumkis, Dmitry; Cheng, Anchi Journal of Structural Biology, Vol. 169, Issue 3 https://doi.org/10.1016/j.jsb.2009.12.005	journal	March 2010
Structural principles controlling HIV envelope glycosylation Behrens, Anna-Janina; Crispin, Max Current Opinion in Structural Biology, Vol. 44 https://doi.org/10.1016/j.sbi.2017.03.008	journal	June 2017
Insights into the trimeric HIV-1 envelope glycoprotein structure Ward, Andrew B.; Wilson, Ian A. Trends in Biochemical Sciences, Vol. 40, Issue 2 https://doi.org/10.1016/j.tibs.2014.12.006	journal	February 2015
Biochemical and biophysical comparison of cleaved and uncleaved soluble, trimeric HIV-1 envelope glycoproteins Dey, Antu K.; David, Kathryn B.; Lu, Min Virology, Vol. 385, Issue 1 https://doi.org/10.1016/j.virol.2008.12.009	journal	March 2009
Accurate determination of local defocus and specimen tilt in electron microscopy Mindell, Joseph A.; Grigorieff, Nikolaus Journal of Structural Biology, Vol. 142, Issue 3 https://doi.org/10.1016/s1047-8477(03)00069-8	journal	June 2003
High-Throughput Thermal Scanning: A General, Rapid Dye-Binding Thermal Shift Screen for Protein Engineering Lavinder, Jason J.; Hari, Sanjay B.; Sullivan, Brandon J. Journal of the American Chemical Society, Vol. 131, Issue 11 https://doi.org/10.1021/ja8049063	journal	March 2009
Prevention of overfitting in cryo-EM structure determination Scheres, Sjors H. W.; Chen, Shaoxia Nature Methods, Vol. 9, Issue 9 https://doi.org/10.1038/nmeth.2115	journal	July 2012
Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM Li, Xueming; Mooney, Paul; Zheng, Shawn Nature Methods, Vol. 10, Issue 6 https://doi.org/10.1038/nmeth.2472	journal	May 2013
An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability van Gils, Marit J.; van den Kerkhof, Tom L. G. M.; Ozorowski, Gabriel Nature Microbiology, Vol. 2, Issue 2 https://doi.org/10.1038/nmicrobiol.2016.199	journal	November 2016
Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site Gristick, Harry B.; von Boehmer, Lotta; West Jr, Anthony P. Nature Structural & Molecular Biology, Vol. 23, Issue 10 https://doi.org/10.1038/nsmb.3291	journal	September 2016
Mechanism of high-mannose N-glycan breakdown and metabolism by Bifidobacterium longum Cordeiro, Rosa L.; Santos, Camila R.; Domingues, Mariane N. Nature Chemical Biology, Vol. 19, Issue 2 https://doi.org/10.1038/s41589-022-01202-4	journal	November 2022
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
Progress in the rational design of an AIDS vaccine Nabel, Gary J.; Kwong, Peter D.; Mascola, John R. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 366, Issue 1579 https://doi.org/10.1098/rstb.2011.0096	journal	October 2011
The glycosylation of human immunodeficiency virus type 1 transmembrane glycoprotein (gp41) is important for the efficient intracellular transport of the envelope precursor gp160 Fenouillet, E.; Jones, I. M. Journal of General Virology, Vol. 76, Issue 6 https://doi.org/10.1099/0022-1317-76-6-1509	journal	June 1995
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/s0021889807021206	journal	July 2007
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/s0907444904019158	journal	November 2004
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/s0907444909042073	journal	December 2009
Complete epitopes for vaccine design derived from a crystal structure of the broadly neutralizing antibodies PGT128 and 8ANC195 in complex with an HIV-1 Env trimer Kong, Leopold; Torrents de la Peña, Alba; Deller, Marc C. Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 10 https://doi.org/10.1107/s1399004715013917	journal	September 2015
A Bayesian view on cryo-EM structure determination Scheres, Sjors H. W. 2012 IEEE 9th International Symposium on Biomedical Imaging (ISBI 2012), 2012 9th IEEE International Symposium on Biomedical Imaging (ISBI) https://doi.org/10.1109/isbi.2012.6235807	conference	May 2012
The HIV-1 envelope glycoprotein structure: nailing down a moving target Ward, Andrew B.; Wilson, Ian A. Immunological Reviews, Vol. 275, Issue 1 https://doi.org/10.1111/imr.12507	journal	January 2017
Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01 Zhou, T.; Georgiev, I.; Wu, X. Science, Vol. 329, Issue 5993 https://doi.org/10.1126/science.1192819	journal	July 2010
Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing Wu, X.; Zhou, T.; Zhu, J. Science, Vol. 333, Issue 6049 https://doi.org/10.1126/science.1207532	journal	August 2011
Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization Georgiev, I. S.; Doria-Rose, N. A.; Zhou, T. Science, Vol. 340, Issue 6133 https://doi.org/10.1126/science.1233989	journal	May 2013
Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions Munro, J. B.; Gorman, J.; Ma, X. Science, Vol. 346, Issue 6210 https://doi.org/10.1126/science.1254426	journal	October 2014
Neutralization of the AIDS retrovirus by antibodies to a recombinant envelope glycoprotein Lasky, L.; Groopman, J.; Fennie, C. Science, Vol. 233, Issue 4760 https://doi.org/10.1126/science.3014647	journal	July 1986
Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer Lee, J. H.; Ozorowski, G.; Ward, A. B. Science, Vol. 351, Issue 6277 https://doi.org/10.1126/science.aad2450	journal	March 2016
HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen Jardine, J. G.; Kulp, D. W.; Havenar-Daughton, C. Science, Vol. 351, Issue 6280 https://doi.org/10.1126/science.aad9195	journal	March 2016
Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody Kong, R.; Xu, K.; Zhou, T. Science, Vol. 352, Issue 6287 https://doi.org/10.1126/science.aae0474	journal	May 2016
Cell- and Protein-Directed Glycosylation of Native Cleaved HIV-1 Envelope Pritchard, Laura K.; Harvey, David J.; Bonomelli, Camille Journal of Virology, Vol. 89, Issue 17 https://doi.org/10.1128/jvi.01190-15	journal	June 2015
Influences on the Design and Purification of Soluble, Recombinant Native-Like HIV-1 Envelope Glycoprotein Trimers Ringe, Rajesh P.; Yasmeen, Anila; Ozorowski, Gabriel Journal of Virology, Vol. 89, Issue 23 https://doi.org/10.1128/jvi.01768-15	journal	August 2015
Molecular Architecture of the Cleavage-Dependent Mannose Patch on a Soluble HIV-1 Envelope Glycoprotein Trimer Behrens, Anna-Janina; Harvey, David J.; Milne, Emilia Journal of Virology, Vol. 91, Issue 2 https://doi.org/10.1128/jvi.01894-16	journal	November 2016
Structure, Receptor Binding, and Antigenicity of Influenza Virus Hemagglutinins from the 1957 H2N2 Pandemic Xu, R.; McBride, R.; Paulson, J. C. Journal of Virology, Vol. 84, Issue 4 https://doi.org/10.1128/jvi.02162-09	journal	December 2009
Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein. Earl, P. L.; Moss, B.; Doms, R. W. Journal of Virology, Vol. 65, Issue 4 https://doi.org/10.1128/jvi.65.4.2047-2055.1991	journal	January 1991
A Recombinant Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits Is an Antigenic Mimic of the Trimeric Virion-Associated Structure Binley, J. M.; Sanders, R. W.; Clas, B. Journal of Virology, Vol. 74, Issue 2 https://doi.org/10.1128/jvi.74.2.627-643.2000	journal	January 2000
A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies Sanders, Rogier W.; Derking, Ronald; Cupo, Albert PLoS Pathogens, Vol. 9, Issue 9, Article No. e1003618 https://doi.org/10.1371/journal.ppat.1003618	journal	September 2013
Well-Ordered Trimeric HIV-1 Subtype B and C Soluble Spike Mimetics Generated by Negative Selection Display Native-like Properties Guenaga, Javier; de Val, Natalia; Tran, Karen PLoS Pathogens, Vol. 11, Issue 1 https://doi.org/10.1371/journal.ppat.1004570	journal	January 2015
Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer Derking, Ronald; Ozorowski, Gabriel; Sliepen, Kwinten PLOS Pathogens, Vol. 11, Issue 3 https://doi.org/10.1371/journal.ppat.1004767	journal	March 2015
Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort Landais, Elise; Huang, Xiayu; Havenar-Daughton, Colin PLOS Pathogens, Vol. 12, Issue 1 https://doi.org/10.1371/journal.ppat.1005369	journal	January 2016
Minimally Mutated HIV-1 Broadly Neutralizing Antibodies to Guide Reductionist Vaccine Design Jardine, Joseph G.; Sok, Devin; Julien, Jean-Philippe PLOS Pathogens, Vol. 12, Issue 8 https://doi.org/10.1371/journal.ppat.1005815	journal	August 2016
Structure and immune recognition of trimeric pre-fusion HIV-1 Env B., Munro, James; Lynn, Morris,; Tongqing, Zhou, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/bt86-bx50	text	January 2014
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
FREAD revisited: Accurate loop structure prediction using a database search algorithm: Loop Structure Prediction Using a Database Search Choi, Yoonjoo; Deane, Charlotte M. Proteins: Structure, Function, and Bioinformatics, Vol. 78, Issue 6 https://doi.org/10.1002/prot.22658	journal	November 2009
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6 https://doi.org/10.1007/s00775-020-01814-y	journal	August 2020
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Accurate determination of local defocus and specimen tilt in electron microscopy Mindell, Joseph A.; Grigorieff, Nikolaus Journal of Structural Biology, Vol. 142, Issue 3 https://doi.org/10.1016/S1047-8477(03)00069-8	journal	June 2003
Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein Behrens, Anna-Janina; Vasiljevic, Snezana; Pritchard, Laura K. Cell Reports, Vol. 14, Issue 11 https://doi.org/10.1016/j.celrep.2016.02.058	journal	March 2016
Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans Garces, Fernando; Lee, Jeong Hyun; de Val, Natalia Immunity, Vol. 43, Issue 6 https://doi.org/10.1016/j.immuni.2015.11.007	journal	December 2015
Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein Guenaga, Javier; Garces, Fernando; de Val, Natalia Immunity, Vol. 46, Issue 5 https://doi.org/10.1016/j.immuni.2017.04.014	journal	May 2017
A Bayesian View on Cryo-EM Structure Determination Scheres, Sjors H. W. Journal of Molecular Biology, Vol. 415, Issue 2 https://doi.org/10.1016/j.jmb.2011.11.010	journal	January 2012
H1 and H7 influenza haemagglutinin structures extend a structural classification of haemagglutinin subtypes Russell, R. J.; Gamblin, S. J.; Haire, L. F. Virology, Vol. 325, Issue 2 https://doi.org/10.1016/j.virol.2004.04.040	journal	August 2004
PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data Roe, Daniel R.; Cheatham, Thomas E. Journal of Chemical Theory and Computation, Vol. 9, Issue 7 https://doi.org/10.1021/ct400341p	journal	June 2013
Development of a Single Column Method for the Separation of Lipid- and Protein-Derived Oligosaccharides Neville, David C. A.; Dwek, Raymond A.; Butters, Terry D. Journal of Proteome Research, Vol. 8, Issue 2 https://doi.org/10.1021/pr800704t	journal	February 2009
Structure and immune recognition of trimeric pre-fusion HIV-1 Env Pancera, Marie; Zhou, Tongqing; Druz, Aliaksandr Nature, Vol. 514, Issue 7523 https://doi.org/10.1038/nature13808	journal	October 2014
Open and closed structures reveal allostery and pliability in the HIV-1 envelope spike Ozorowski, Gabriel; Pallesen, Jesper; de Val, Natalia Nature, Vol. 547, Issue 7663 https://doi.org/10.1038/nature23010	journal	July 2017
The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability Niesen, Frank H.; Berglund, Helena; Vedadi, Masoud Nature Protocols, Vol. 2, Issue 9 https://doi.org/10.1038/nprot.2007.321	journal	September 2007
Structure–function relationships of HIV-1 envelope sequence-variable regions refocus vaccine design Zolla-Pazner, Susan; Cardozo, Timothy Nature Reviews Immunology, Vol. 10, Issue 7 https://doi.org/10.1038/nri2801	journal	July 2010
Privateer: software for the conformational validation of carbohydrate structures Agirre, Jon; Iglesias-Fernández, Javier; Rovira, Carme Nature Structural & Molecular Biology, Vol. 22, Issue 11 https://doi.org/10.1038/nsmb.3115	journal	November 2015
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding Panico, Maria; Bouché, Laura; Binet, Daniel Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep32956	journal	September 2016
Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120 West, Anthony P.; Diskin, Ron; Nussenzweig, Michel C. Proceedings of the National Academy of Sciences, Vol. 109, Issue 30 https://doi.org/10.1073/pnas.1208984109	journal	June 2012
Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation Ringe, R. P.; Sanders, R. W.; Yasmeen, A. Proceedings of the National Academy of Sciences, Vol. 110, Issue 45 https://doi.org/10.1073/pnas.1314351110	journal	October 2013
Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo Medina-Ramírez, Max; Garces, Fernando; Escolano, Amelia The Journal of Experimental Medicine, Vol. 214, Issue 9 https://doi.org/10.1084/jem.20161160	journal	August 2017
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Complete epitopes for vaccine design derived from a crystal structure of the broadly neutralizing antibodies PGT128 and 8ANC195 in complex with an HIV-1 Env trimer Kong, Leopold; Torrents de la Peña, Alba; Deller, Marc C. Acta Crystallographica Section D Biological Crystallography, Vol. 71, Issue 10 https://doi.org/10.1107/S1399004715013917	journal	September 2015
Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer Julien, J. -P.; Cupo, A.; Sok, D. Science, Vol. 342, Issue 6165 https://doi.org/10.1126/science.1245625	journal	October 2013
Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer Lyumkis, D.; Julien, J. -P.; de Val, N. Science, Vol. 342, Issue 6165 https://doi.org/10.1126/science.1245627	journal	October 2013
HIV-1 neutralizing antibodies induced by native-like envelope trimers Sanders, R. W.; van Gils, M. J.; Derking, R. Science, Vol. 349, Issue 6244 https://doi.org/10.1126/science.aac4223	journal	June 2015
Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen Jardine, J. G.; Ota, T.; Sok, D. Science, Vol. 349, Issue 6244 https://doi.org/10.1126/science.aac5894	journal	June 2015
Cell- and Protein-Directed Glycosylation of Native Cleaved HIV-1 Envelope Pritchard, Laura K.; Harvey, David J.; Bonomelli, Camille Journal of Virology, Vol. 89, Issue 17 https://doi.org/10.1128/JVI.01190-15	journal	June 2015
Influences on the Design and Purification of Soluble, Recombinant Native-Like HIV-1 Envelope Glycoprotein Trimers Ringe, Rajesh P.; Yasmeen, Anila; Ozorowski, Gabriel Journal of Virology, Vol. 89, Issue 23 https://doi.org/10.1128/JVI.01768-15	journal	August 2015
Structure, Receptor Binding, and Antigenicity of Influenza Virus Hemagglutinins from the 1957 H2N2 Pandemic Xu, R.; McBride, R.; Paulson, J. C. Journal of Virology, Vol. 84, Issue 4 https://doi.org/10.1128/JVI.02162-09	journal	December 2009
Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein. Earl, P. L.; Moss, B.; Doms, R. W. Journal of Virology, Vol. 65, Issue 4 https://doi.org/10.1128/JVI.65.4.2047-2055.1991	journal	January 1991
A Recombinant Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits Is an Antigenic Mimic of the Trimeric Virion-Associated Structure Binley, J. M.; Sanders, R. W.; Clas, B. Journal of Virology, Vol. 74, Issue 2 https://doi.org/10.1128/JVI.74.2.627-643.2000	journal	January 2000
Stabilization of the Soluble, Cleaved, Trimeric Form of the Envelope Glycoprotein Complex of Human Immunodeficiency Virus Type 1 Sanders, R. W.; Vesanen, M.; Schuelke, N. Journal of Virology, Vol. 76, Issue 17, p. 8875-8889 https://doi.org/10.1128/JVI.76.17.8875-8889.2002	journal	September 2002
Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits Yasmeen, Anila; Ringe, Rajesh; Derking, Ronald Retrovirology, Vol. 11, Issue 1 https://doi.org/10.1186/1742-4690-11-41	journal	January 2014
Structural basis for germline gene usage of a potent class of antibodies targeting the CD4 binding site of HIV-1 gp120 West, Ap; Diskin, R.; Nussenzweig, Mc Retrovirology, Vol. 9, Issue S2 https://doi.org/10.1186/1742-4690-9-s2-o33	journal	September 2012
Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans Julien, Jean-Philippe; Sok, Devin; Khayat, Reza PLoS Pathogens, Vol. 9, Issue 5 https://doi.org/10.1371/journal.ppat.1003342	journal	May 2013

Cited By (13)

Glycosylation of viral surface proteins probed by mass spectrometry Hargett, Audra A.; Renfrow, Matthew B. Current Opinion in Virology, Vol. 36 https://doi.org/10.1016/j.coviro.2019.05.003	journal	June 2019
Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability Dubrovskaya, Viktoriya; Tran, Karen; Ozorowski, Gabriel Immunity, Vol. 51, Issue 5 https://doi.org/10.1016/j.immuni.2019.10.008	journal	November 2019
Protein and Glycan Mimicry in HIV Vaccine Design Seabright, Gemma E.; Doores, Katie J.; Burton, Dennis R. Journal of Molecular Biology, Vol. 431, Issue 12 https://doi.org/10.1016/j.jmb.2019.04.016	journal	May 2019
Capturing the inherent structural dynamics of the HIV-1 envelope glycoprotein fusion peptide Kumar, Sonu; Sarkar, Anita; Pugach, Pavel Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-08738-5	journal	February 2019
Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence Sliepen, Kwinten; Han, Byung Woo; Bontjer, Ilja Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-10262-5	journal	May 2019
Strategies for inducing effective neutralizing antibody responses against HIV-1 del Moral-Sánchez, Iván; Sliepen, Kwinten Expert Review of Vaccines, Vol. 18, Issue 11 https://doi.org/10.1080/14760584.2019.1690458	journal	November 2019
The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases Izaguirre, Gonzalo Viruses, Vol. 11, Issue 9 https://doi.org/10.3390/v11090837	journal	September 2019
Chemokine-Adjuvanted Plasmid DNA Induces Homing of Antigen-Specific and Non–Antigen-Specific B and T Cells to the Intestinal and Genital Mucosae Aldon, Yoann; Kratochvil, Sven; Shattock, Robin J. The Journal of Immunology, Vol. 204, Issue 4 https://doi.org/10.4049/jimmunol.1901184	journal	January 2020
An Engineered Biomimetic MPER Peptide Vaccine Induces Weakly HIV Neutralizing Antibodies in Mice Shao, Shuai; Huang, Wei-Chiao; Lin, Cuiyan Annals of Biomedical Engineering, Vol. 48, Issue 7 https://doi.org/10.1007/s10439-019-02398-8	journal	December 2019
An MPER antibody neutralizes HIV-1 using germline features shared among donors Zhang, Lei; Irimia, Adriana; He, Lingling Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-12973-1	journal	November 2019
Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements Henderson, Rory; Lu, Maolin; Zhou, Ye Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-019-14196-w	journal	January 2020
Stabilized diverse HIV-1 envelope trimers for vaccine design Wang, Qian; Ma, Bingting; Liang, Qingtai Emerging Microbes & Infections, Vol. 9, Issue 1 https://doi.org/10.1080/22221751.2020.1745093	journal	January 2020
Stabilized diverse HIV-1 envelope trimers for vaccine design Wang, Qian; Ma, Bingting; Liang, Qingtai Taylor & Francis https://doi.org/10.6084/m9.figshare.12091959	text	January 2020

Similar Records

Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability

Journal Article · Mon Nov 11 19:00:00 EST 2019 · Immunity · OSTI ID:1577147

Structural characterization of a highly-potent V3-glycan broadly neutralizing antibody bound to natively-glycosylated HIV-1 envelope

Journal Article · Tue Mar 27 20:00:00 EDT 2018 · Nature Communications · OSTI ID:1624084

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Glycosylation
HIV infections
Vaccines
X-ray crystallography

Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer

Citation Formats

References (94)

Cited By (13)

Similar Records

Related Subjects