Receptor Activation of HIV-1 Env Leads to Asymmetric Exposure of the gp41 Trimer

Khasnis, Mukta D.; Halkidis, Konstantine; Bhardwaj, Anshul; Root, Michael J.; Trkola, Alexandra

doi:10.1371/journal.ppat.1006098

Title: Receptor Activation of HIV-1 Env Leads to Asymmetric Exposure of the gp41 Trimer

Journal Article · Mon Dec 19 00:00:00 EST 2016 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1006098· OSTI ID:1368229

Khasnis, Mukta D. ^[1];

^[1];

^[1]; Trkola, Alexandra ^[1]

Thomas Jefferson Univ., Philadelphia, PA (United States). Sidney Kimmel Cancer Center, Dept. of Biochemistry and Molecular Biology

Structural rearrangements of HIV-1 glycoprotein Env promote viral entry through membrane fusion. Env is a symmetric homotrimer with each protomer composed of surface subunit gp120 and transmembrane subunit gp41. Cellular CD4- and chemokine receptor-binding to gp120 coordinate conformational changes in gp41, first to an extended prehairpin intermediate (PHI) and, ultimately, into a fusogenic trimer-of-hairpins (TOH). HIV-1 fusion inhibitors target gp41 in the PHI and block TOH formation. To characterize structural transformations into and through the PHI, we employed asymmetric Env trimers containing both high and low affinity binding sites for individual fusion inhibitors. Asymmetry was achieved using engineered Env heterotrimers composed of protomers deficient in either CD4- or chemokine receptor-binding. Linking receptor engagement to inhibitor affinity allowed us to assess conformational changes of individual Env protomers in the context of a functioning trimer. We found that the transition into the PHI could occur symmetrically or asymmetrically depending on the stoichiometry of CD4 binding. Sequential engagement of multiple CD4s promoted progressive exposure of individual fusion inhibitor binding sites in a CD4-dependent fashion. By contrast, engagement of only a single CD4 molecule led to a delayed, but symmetric, exposure of the gp41 trimer. This complex coupling between Env-CD4 interaction and gp41 exposure explained the multiphasic fusion-inhibitor titration observed for a mutant Env homotrimer with a naturally asymmetric gp41. Our results suggest that the spatial and temporal exposure of gp41 can proceed in a nonconcerted, asymmetric manner depending on the number of CD4s that engage the Env trimer. The findings have important implications for the mechanism of viral membrane fusion and the development of vaccine candidates designed to elicit neutralizing antibodies targeting gp41 in the PHI.

View Accepted Manuscript (DOE)

Cite

Export

Save

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

Sponsoring Organization:: National Institutes of Health (NIH); American Foundation for AIDS Research

Grant/Contract Number:: R01 GM066682; T32 GM100836; 02856-31-RGT

OSTI ID:: 1368229

Journal Information:: PLoS Pathogens, Vol. 12, Issue 12; ISSN 1553-7374

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 24 works

Citation information provided by
Web of Science

References (90)

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
Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env Do Kwon, Young; Pancera, Marie; Acharya, Priyamvada Nature Structural & Molecular Biology, Vol. 22, Issue 7 https://doi.org/10.1038/nsmb.3051	journal	June 2015
Dilation of the Human Immunodeficiency Virus–1 Envelope Glycoprotein Fusion Pore Revealed by the Inhibitory Action of a Synthetic Peptide from gp41 Muñoz-Barroso, Isabel; Durell, Stewart; Sakaguchi, Kazuyasu Journal of Cell Biology, Vol. 140, Issue 2 https://doi.org/10.1083/jcb.140.2.315	journal	January 1998
A Trimeric Structural Subdomain of the HIV-1 Transmembrane Glycoprotein Lu, Min; Kim, Peter S. Journal of Biomolecular Structure and Dynamics, Vol. 15, Issue 3 https://doi.org/10.1080/07391102.1997.10508958	journal	December 1997
Immunogenic Presentation of a Conserved gp41 Epitope of Human Immunodeficiency Virus Type 1 on Recombinant Surface Antigen of Hepatitis B Virus Eckhart, L.; Raffelsberger, W.; Ferko, B. Journal of General Virology, Vol. 77, Issue 9 https://doi.org/10.1099/0022-1317-77-9-2001	journal	September 1996
Structure of an unliganded simian immunodeficiency virus gp120 core Chen, Bing; Vogan, Erik M.; Gong, Haiyun Nature, Vol. 433, Issue 7028 https://doi.org/10.1038/nature03327	journal	February 2005
New methods for indexing multi-lattice diffraction data Gildea, Richard J.; Waterman, David G.; Parkhurst, James M. Acta Crystallographica Section D Biological Crystallography, Vol. 70, Issue 10 https://doi.org/10.1107/S1399004714017039	journal	September 2014
Molecular Architectures of Trimeric SIV and HIV-1 Envelope Glycoproteins on Intact Viruses: Strain-Dependent Variation in Quaternary Structure White, Tommi A.; Bartesaghi, Alberto; Borgnia, Mario J. PLoS Pathogens, Vol. 6, Issue 12 https://doi.org/10.1371/journal.ppat.1001249	journal	December 2010
Atomic structure of the ectodomain from HIV-1 gp41 Weissenhorn, W.; Dessen, A.; Harrison, S. C. Nature, Vol. 387, Issue 6631 https://doi.org/10.1038/387426a0	journal	May 1997
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
Characterization of the steric defense of the HIV‐1 gp41 N‐trimer region Eckert, Debra M.; Shi, Yu; Kim, Sunghwan Protein Science, Vol. 17, Issue 12 https://doi.org/10.1110/ps.038273.108	journal	December 2008
Asymmetric Deactivation of HIV-1 gp41 following Fusion Inhibitor Binding Kahle, Kristen M.; Steger, H. Kirby; Root, Michael J. PLoS Pathogens, Vol. 5, Issue 11 https://doi.org/10.1371/journal.ppat.1000674	journal	November 2009
Epitope Mapping and Topology of Baculovirus-Expressed HIV-1 gp160 Determined with a Panel of Murine Monoclonal Antibodies Abacioglu, Yusuf Hakan; Fouts, Timothy R.; Laman, Jon D. AIDS Research and Human Retroviruses, Vol. 10, Issue 4 https://doi.org/10.1089/aid.1994.10.371	journal	April 1994
Membrane Fusion Mediated by Human Immunodeficiency Virus Envelope Glycoprotein Melikyan, Gregory B. Current Topics in Membranes https://doi.org/10.1016/B978-0-12-385891-7.00004-0	book	January 2011
Dissociation of gp120 from HIV-1 virions induced by soluble CD4 Moore, J.; McKeating, J.; Weiss, R. Science, Vol. 250, Issue 4984 https://doi.org/10.1126/science.2251501	journal	November 1990
A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope Miller, M. D.; Geleziunas, R.; Bianchi, E. Proceedings of the National Academy of Sciences, Vol. 102, Issue 41 https://doi.org/10.1073/pnas.0506927102	journal	October 2005
Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Wild, C. T.; Shugars, D. C.; Greenwell, T. K. Proceedings of the National Academy of Sciences, Vol. 91, Issue 21 https://doi.org/10.1073/pnas.91.21.9770	journal	October 1994
Subunit Stoichiometry of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers during Virus Entry into Host Cells Yang, X.; Kurteva, S.; Ren, X. Journal of Virology, Vol. 80, Issue 9 https://doi.org/10.1128/JVI.80.9.4388-4395.2006	journal	April 2006
Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody Kwong, Peter D.; Wyatt, Richard; Robinson, James Nature, Vol. 393, Issue 6686 https://doi.org/10.1038/31405	journal	June 1998
Vaccination with peptide mimetics of the gp41 prehairpin fusion intermediate yields neutralizing antisera against HIV-1 isolates Bianchi, E.; Joyce, J. G.; Miller, M. D. Proceedings of the National Academy of Sciences, Vol. 107, Issue 23 https://doi.org/10.1073/pnas.1004261107	journal	May 2010
Identification of a major co-receptor for primary isolates of HIV-1 Deng, HongKui; Liu, Rong; Ellmeier, Wilfried Nature, Vol. 381, Issue 6584 https://doi.org/10.1038/381661a0	journal	June 1996
Cooperative subunit interactions within the oligomeric envelope glycoprotein of HIV-1: Functional complementation of specific defects in gp120 and gp41 Salzwedel, K.; Berger, E. A. Proceedings of the National Academy of Sciences, Vol. 97, Issue 23 https://doi.org/10.1073/pnas.230438497	journal	October 2000
How good are my data and what is the resolution? Evans, Philip R.; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7 https://doi.org/10.1107/S0907444913000061	journal	June 2013
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
Evidence That the Transition of HIV-1 Gp41 into a Six-Helix Bundle, Not the Bundle Configuration, Induces Membrane Fusion Melikyan, Grigory B.; Markosyan, Ruben M.; Hemmati, Hila Journal of Cell Biology, Vol. 151, Issue 2 https://doi.org/10.1083/jcb.151.2.413	journal	October 2000
Is there a future for antiviral fusion inhibitors? Berkhout, Ben; Eggink, Dirk; Sanders, Rogier W. Current Opinion in Virology, Vol. 2, Issue 1 https://doi.org/10.1016/j.coviro.2012.01.002	journal	February 2012
HIV-1 gp41 as a Target for Viral Entry Inhibition Root, Michael; Steger, H. Current Pharmaceutical Design, Vol. 10, Issue 15 https://doi.org/10.2174/1381612043384448	journal	June 2004
Early Steps of HIV-1 Fusion Define the Sensitivity to Inhibitory Peptides That Block 6-Helix Bundle Formation Miyauchi, Kosuke; Kozlov, Michael M.; Melikyan, Gregory B. PLoS Pathogens, Vol. 5, Issue 9 https://doi.org/10.1371/journal.ppat.1000585	journal	September 2009
HIV-1 Envelope Proteins Complete Their Folding into Six-helix Bundles Immediately after Fusion Pore Formation Markosyan, Ruben M.; Cohen, Fredric S.; Melikyan, Grigory B. Molecular Biology of the Cell, Vol. 14, Issue 3 https://doi.org/10.1091/mbc.E02-09-0573	journal	March 2003
MPER-specific antibodies induce gp120 shedding and irreversibly neutralize HIV-1 Ruprecht, Claudia R.; Krarup, Anders; Reynell, Lucy The Journal of Experimental Medicine, Vol. 208, Issue 3 https://doi.org/10.1084/jem.20101907	journal	February 2011
Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41 Montgomery, Donna L.; Wang, Ying-Jie; Hrin, Renee mAbs, Vol. 1, Issue 5 https://doi.org/10.4161/mabs.1.5.9214	journal	September 2009
Core Structure of gp41 from the HIV Envelope Glycoprotein Chan, David C.; Fass, Deborah; Berger, James M. Cell, Vol. 89, Issue 2 https://doi.org/10.1016/S0092-8674(00)80205-6	journal	April 1997
Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics Reeves, J. D.; Gallo, S. A.; Ahmad, N. Proceedings of the National Academy of Sciences, Vol. 99, Issue 25 https://doi.org/10.1073/pnas.252469399	journal	November 2002
CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5 Wu, Lijun; Gerard, Norma P.; Wyatt, Richard Nature, Vol. 384, Issue 6605 https://doi.org/10.1038/384179a0	journal	November 1996
Thermodynamic Stability of the Asymmetric Doubly-Ligated Hemoglobin Tetramer (α ^+CN β ^+CN )(αβ): Methodological and Mechanistic Issues ^† Ackers, Gary K.; Perrella, Michele; Holt, Jo M. Biochemistry, Vol. 36, Issue 36 https://doi.org/10.1021/bi971382x	journal	September 1997
Affinity maturation by targeted diversification of the CDR-H2 loop of a monoclonal Fab derived from a synthetic naïve human antibody library and directed against the internal trimeric coiled-coil of gp41 yields a set of Fabs with improved HIV-1 neutralization potency and breadth Gustchina, Elena; Louis, John M.; Frisch, Christian Virology, Vol. 393, Issue 1 https://doi.org/10.1016/j.virol.2009.07.019	journal	October 2009
Antibody elicited against the gp41 N-heptad repeat (NHR) coiled-coil can neutralize HIV-1 with modest potency but non-neutralizing antibodies also bind to NHR mimetics Nelson, Josh D.; Kinkead, Heather; Brunel, Florence M. Virology, Vol. 377, Issue 1 https://doi.org/10.1016/j.virol.2008.04.005	journal	July 2008
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
Viral membrane fusion Harrison, Stephen C. Nature Structural & Molecular Biology, Vol. 15, Issue 7 https://doi.org/10.1038/nsmb.1456	journal	July 2008
Interaction of the gp120 V1V2 loop with a neighboring gp120 unit shields the HIV envelope trimer against cross-neutralizing antibodies Rusert, Peter; Krarup, Anders; Magnus, Carsten The Journal of Experimental Medicine, Vol. 208, Issue 7 https://doi.org/10.1084/jem.20110196	journal	June 2011
CHEMOKINE RECEPTORS AS HIV-1 CORECEPTORS: Roles in Viral Entry, Tropism, and Disease Berger, Edward A.; Murphy, Philip M.; Farber, Joshua M. Annual Review of Immunology, Vol. 17, Issue 1 https://doi.org/10.1146/annurev.immunol.17.1.657	journal	April 1999
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
Complementation of diverse HIV-1 Env defects through cooperative subunit interactions: a general property of the functional trimer Salzwedel, Karl; Berger, Edward A. Retrovirology, Vol. 6, Issue 1 https://doi.org/10.1186/1742-4690-6-75	journal	August 2009
Evidence that a prominent cavity in the coiled coil of HIV type 1 gp41 is an attractive drug target Chan, D. C.; Chutkowski, C. T.; Kim, P. S. Proceedings of the National Academy of Sciences, Vol. 95, Issue 26 https://doi.org/10.1073/pnas.95.26.15613	journal	December 1998
Fusion Peptides Derived from the HIV Type 1 Glycoprotein 41 Associate within Phospholipid Membranes and Inhibit Cell-Cell Fusion: STRUCTURE-FUNCTION STUDY Kliger, Yossef; Aharoni, Amir; Rapaport, Doron Journal of Biological Chemistry, Vol. 272, Issue 21 https://doi.org/10.1074/jbc.272.21.13496	journal	May 1997
Spectroscopic Determination of Tryptophan and Tyrosine in Proteins ^* Edelhoch, Harold Biochemistry, Vol. 6, Issue 7 https://doi.org/10.1021/bi00859a010	journal	July 1967
Protein Design of an HIV-1 Entry Inhibitor Root, M. J. Science, Vol. 291, Issue 5505 https://doi.org/10.1126/science.1057453	journal	January 2001
Kinetic Factors Control Efficiencies of Cell Entry, Efficacies of Entry Inhibitors, and Mechanisms of Adaptation of Human Immunodeficiency Virus Platt, E. J.; Durnin, J. P.; Kabat, D. Journal of Virology, Vol. 79, Issue 7 https://doi.org/10.1128/JVI.79.7.4347-4356.2005	journal	March 2005
Capture of an early fusion-active conformation of HIV-1 gp41 Furuta, Rika A.; Wild, Carl T.; Weng, Yongkai Nature Structural Biology, Vol. 5, Issue 4 https://doi.org/10.1038/nsb0498-276	journal	April 1998
The Role of Antibody Polyspecificity and Lipid Reactivity in Binding of Broadly Neutralizing Anti-HIV-1 Envelope Human Monoclonal Antibodies 2F5 and 4E10 to Glycoprotein 41 Membrane Proximal Envelope Epitopes Alam, S. Munir; McAdams, Mildred; Boren, David The Journal of Immunology, Vol. 178, Issue 7 https://doi.org/10.4049/jimmunol.178.7.4424	journal	March 2007
Molecular architecture of native HIV-1 gp120 trimers Liu, Jun; Bartesaghi, Alberto; Borgnia, Mario J. Nature, Vol. 455, Issue 7209 https://doi.org/10.1038/nature07159	journal	July 2008
Conformational changes induced in the human immunodeficiency virus envelope glycoprotein by soluble CD4 binding. Sattentau, Q. J.; Moore, J. P. The Journal of Experimental Medicine, Vol. 174, Issue 2 https://doi.org/10.1084/jem.174.2.407	journal	August 1991
Biochemistry and Biophysics of HIV-1 gp41 - Membrane Interactions and Implications for HIV-1 Envelope Protein Mediated Viral-Cell Fusion and Fusion Inhibitor Design Cai, Lifeng; Gochin, Miriam; Liu, Keliang Current Topics in Medicinal Chemistry, Vol. 11, Issue 24 https://doi.org/10.2174/156802611798808497	journal	December 2011
Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution Wilson, I. A.; Skehel, J. J.; Wiley, D. C. Nature, Vol. 289, Issue 5796 https://doi.org/10.1038/289366a0	journal	January 1981
Cryo-Electron Tomographic Structure of an Immunodeficiency Virus Envelope Complex In Situ Zanetti, Giulia; Briggs, John A. G.; Grünewald, Kay PLoS Pathogens, Vol. 2, Issue 8 https://doi.org/10.1371/journal.ppat.0020083	journal	January 2006
Inhibiting HIV-1 Entry Eckert, Debra M.; Malashkevich, Vladimir N.; Hong, Lily H. Cell, Vol. 99, Issue 1 https://doi.org/10.1016/S0092-8674(00)80066-5	journal	October 1999
The role of the N-terminal segment of CCR5 in HIV-1 Env-mediated membrane fusion and the mechanism of virus adaptation to CCR5 lacking this segment Melikyan, Gregory B.; Platt, Emily J.; Kabat, David Retrovirology, Vol. 4, Issue 1 https://doi.org/10.1186/1742-4690-4-55	journal	January 2007
Mechanisms of Viral Membrane Fusion and Its Inhibition Eckert, Debra M.; Kim, Peter S. Annual Review of Biochemistry, Vol. 70, Issue 1 https://doi.org/10.1146/annurev.biochem.70.1.777	journal	June 2001
Crystal Structure of HIV-1 gp41 Including Both Fusion Peptide and Membrane Proximal External Regions Buzon, Victor; Natrajan, Ganesh; Schibli, David PLoS Pathogens, Vol. 6, Issue 5 https://doi.org/10.1371/journal.ppat.1000880	journal	May 2010
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
A synthetic peptide inhibitor of human immunodeficiency virus replication: correlation between solution structure and viral inhibition. Wild, C.; Oas, T.; McDanal, C. Proceedings of the National Academy of Sciences, Vol. 89, Issue 21 https://doi.org/10.1073/pnas.89.21.10537	journal	November 1992
Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor Lee, Jeffrey E.; Fusco, Marnie L.; Hessell, Ann J. Nature, Vol. 454, Issue 7201 https://doi.org/10.1038/nature07082	journal	July 2008
Design of a Potent D-Peptide HIV-1 Entry Inhibitor with a Strong Barrier to Resistance Welch, B. D.; Francis, J. N.; Redman, J. S. Journal of Virology, Vol. 84, Issue 21 https://doi.org/10.1128/JVI.01339-10	journal	August 2010
HIV Entry and Its Inhibition Chan, David C.; Kim, Peter S. Cell, Vol. 93, Issue 5 https://doi.org/10.1016/S0092-8674(00)81430-0	journal	May 1998
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
HIV-1 inhibition by a peptide Jiang, Shibo; Lin, Kang; Strick, Nathan Nature, Vol. 365, Issue 6442 https://doi.org/10.1038/365113a0	journal	September 1993
Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding. Olshevsky, U.; Helseth, E.; Furman, C. Journal of Virology, Vol. 64, Issue 12 https://doi.org/10.1128/JVI.64.12.5701-5707.1990	journal	January 1990
Design and Properties of N _CCG -gp41, a Chimeric gp41 Molecule with Nanomolar HIV Fusion Inhibitory Activity Louis, John M.; Bewley, Carole A.; Clore, G. Marius Journal of Biological Chemistry, Vol. 276, Issue 31 https://doi.org/10.1074/jbc.c100317200	journal	June 2001
Early Intermediates in HIV-1 Envelope Glycoprotein-mediated Fusion Triggered by CD4 and Co-receptor Complexes Dimitrov, Antony S.; Xiao, Xiaodong; Dimitrov, Dimiter S. Journal of Biological Chemistry, Vol. 276, Issue 32 https://doi.org/10.1074/jbc.m103788200	journal	June 2001
Kinetic Dependence to HIV-1 Entry Inhibition Steger, H. Kirby; Root, Michael J. Journal of Biological Chemistry, Vol. 281, Issue 35 https://doi.org/10.1074/jbc.m601457200	journal	June 2006
Interactions of HIV-1 Inhibitory Peptide T20 with the gp41 N-HR Coiled Coil Champagne, Kelly; Shishido, Akira; Root, Michael J. Journal of Biological Chemistry, Vol. 284, Issue 6 https://doi.org/10.1074/jbc.m809269200	journal	December 2008
Asymmetric Cooperativity in a Symmetric Tetramer: Human Hemoglobin Ackers, Gary K.; Holt, Jo M. Journal of Biological Chemistry, Vol. 281, Issue 17 https://doi.org/10.1074/jbc.r500019200	journal	January 2006
Receptor-Mediated Activation of Immunodeficiency Viruses in Viral Fusion Allan, Jonathan S. Science, Vol. 252, Issue 5010 https://doi.org/10.1126/science.1925547	journal	May 1991
A Monoclonal Fab Derived from a Human Nonimmune Phage Library Reveals a New Epitope on gp41 and Neutralizes Diverse Human Immunodeficiency Virus Type 1 Strains Gustchina, E.; Louis, J. M.; Lam, S. N. Journal of Virology, Vol. 81, Issue 23 https://doi.org/10.1128/jvi.01260-07	journal	September 2007
Clinical Resistance to Enfuvirtide Does Not Affect Susceptibility of Human Immunodeficiency Virus Type 1 to Other Classes of Entry Inhibitors Ray, N.; Harrison, J. E.; Blackburn, L. A. Journal of Virology, Vol. 81, Issue 7 https://doi.org/10.1128/jvi.02413-06	journal	January 2007
Crystal Structure of Unliganded Influenza B Virus Hemagglutinin Wang, Q.; Cheng, F.; Lu, M. Journal of Virology, Vol. 82, Issue 6 https://doi.org/10.1128/jvi.02477-07	journal	January 2008
Three-Dimensional Structures of Soluble CD4-Bound States of Trimeric Simian Immunodeficiency Virus Envelope Glycoproteins Determined by Using Cryo-Electron Tomography White, T. A.; Bartesaghi, A.; Borgnia, M. J. Journal of Virology, Vol. 85, Issue 23 https://doi.org/10.1128/jvi.05297-11	journal	September 2011
Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: effects on infectivity and neutralization. McKeating, J. A.; McKnight, A.; Moore, J. P. Journal of Virology, Vol. 65, Issue 2 https://doi.org/10.1128/jvi.65.2.852-860.1991	journal	January 1991
Direct measurement of soluble CD4 binding to human immunodeficiency virus type 1 virions: gp120 dissociation and its implications for virus-cell binding and fusion reactions and their neutralization by soluble CD4. Moore, J. P.; McKeating, J. A.; Norton, W. A. Journal of Virology, Vol. 65, Issue 3 https://doi.org/10.1128/jvi.65.3.1133-1140.1991	journal	January 1991
Effects of changes in gp120-CD4 binding affinity on human immunodeficiency virus type 1 envelope glycoprotein function and soluble CD4 sensitivity. Thali, M.; Olshevsky, U.; Furman, C. Journal of Virology, Vol. 65, Issue 9 https://doi.org/10.1128/jvi.65.9.5007-5012.1991	journal	January 1991
Distinct modes of human immunodeficiency virus type 1 proviral latency revealed by superinfection of nonproductively infected cell lines with recombinant luciferase-encoding viruses. Chen, B. K.; Saksela, K.; Andino, R. Journal of Virology, Vol. 68, Issue 2 https://doi.org/10.1128/jvi.68.2.654-660.1994	journal	January 1994
Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. Björndal, A.; Deng, H.; Jansson, M. Journal of virology, Vol. 71, Issue 10 https://doi.org/10.1128/jvi.71.10.7478-7487.1997	journal	January 1997
Macrophage tropism of human immunodeficiency virus type 1 and utilization of the CC-CKR5 coreceptor. Cheng-Mayer, C.; Liu, R.; Landau, N. R. Journal of virology, Vol. 71, Issue 2 https://doi.org/10.1128/jvi.71.2.1657-1661.1997	journal	January 1997
Direct Evidence that C-Peptide Inhibitors of Human Immunodeficiency Virus Type 1 Entry Bind to the gp41 N-Helical Domain in Receptor-Activated Viral Envelope Kilgore, N. R.; Salzwedel, K.; Reddick, M. Journal of Virology, Vol. 77, Issue 13 https://doi.org/10.1128/jvi.77.13.7669-7672.2003	journal	July 2003
Impact of Mutations in the Coreceptor Binding Site on Human Immunodeficiency Virus Type 1 Fusion, Infection, and Entry Inhibitor Sensitivity Reeves, J. D.; Miamidian, J. L.; Biscone, M. J. Journal of Virology, Vol. 78, Issue 10 https://doi.org/10.1128/jvi.78.10.5476-5485.2004	journal	April 2004
Emergence of a Drug-Dependent Human Immunodeficiency Virus Type 1 Variant during Therapy with the T20 Fusion Inhibitor Baldwin, C. E.; Sanders, R. W.; Deng, Y. Journal of Virology, Vol. 78, Issue 22 https://doi.org/10.1128/jvi.78.22.12428-12437.2004	journal	October 2004
The Cytoplasmic Tail Slows the Folding of Human Immunodeficiency Virus Type 1 Env from a Late Prebundle Configuration into the Six-Helix Bundle Abrahamyan, L. G.; Mkrtchyan, S. R.; Binley, J. Journal of Virology, Vol. 79, Issue 1 https://doi.org/10.1128/jvi.79.1.106-115.2005	journal	December 2004
Variants of Human Immunodeficiency Virus Type 1 That Efficiently Use CCR5 Lacking the Tyrosine-Sulfated Amino Terminus Have Adaptive Mutations in gp120, Including Loss of a Functional N-Glycan Platt, E. J.; Shea, D. M.; Rose, P. P. Journal of Virology, Vol. 79, Issue 7 https://doi.org/10.1128/jvi.79.7.4357-4368.2005	journal	March 2005
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

Cited By (8)

Electron diffraction data processing with DIALS Clabbers, Max T. B.; Gruene, Tim; Parkhurst, James M. Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 6 https://doi.org/10.1107/s2059798318007726	journal	May 2018
Mutations That Increase the Stability of the Postfusion gp41 Conformation of the HIV-1 Envelope Glycoprotein Are Selected by both an X4 and R5 HIV-1 Virus To Escape Fusion Inhibitors Corresponding to Heptad Repeat 1 of gp41, but the gp120 Adaptive Mutations Differ between the Two Viruses Zhuang, Min; Vassell, Russell; Yuan, Chen Journal of Virology, Vol. 93, Issue 11 https://doi.org/10.1128/jvi.00142-19	journal	March 2019
CD4 occupancy triggers sequential pre-fusion conformational states of the HIV-1 envelope trimer with relevance for broadly neutralizing antibody activity Ivan, Branislav; Sun, Zhaozhi; Subbaraman, Harini PLOS Biology, Vol. 17, Issue 1 https://doi.org/10.1371/journal.pbio.3000114	journal	January 2019
Massively Parallel Profiling of HIV-1 Resistance to the Fusion Inhibitor Enfuvirtide Dingens, Adam S.; Arenz, Dana; Overbaugh, Julie Viruses, Vol. 11, Issue 5 https://doi.org/10.3390/v11050439	journal	May 2019
HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations Ma, Xiaochu; Lu, Maolin; Gorman, Jason eLife, Vol. 7 https://doi.org/10.7554/elife.34271	journal	March 2018
CD4 occupancy triggers sequential pre-fusion conformational states of the HIV-1 envelope trimer with relevance for broadly neutralizing antibody activity Ivan, Branislav; Sun, Zhaozhi; Subbaraman, Harini Public Library of Science (PLoS) https://doi.org/10.5167/uzh-166639	text	January 2019
Massively parallel profiling of HIV-1 resistance to the fusion inhibitor enfuvirtide Dingens, Adam S.; Arenz, Dana; Overbaugh, Julie https://doi.org/10.1101/472746	posted_content	November 2018
Stoichiometric Analyses of Soluble CD4 to Native-like HIV-1 Envelope by Single-Molecule Fluorescence Spectroscopy Agrawal, Parul; DeVico, Anthony L.; Foulke, James S. Cell Reports, Vol. 29, Issue 1 https://doi.org/10.1016/j.celrep.2019.08.074	journal	October 2019

Similar Records

Dominant-negative effect of hetero-oligomerization on the function of the human immunodeficiency virus type 1 envelope glycoprotein complex

Journal Article · Thu Jul 20 00:00:00 EDT 2006 · Virology · OSTI ID:1368229

Herrera, Carolina; Klasse, Per Johan; Kibler, Christopher W; +3 more

Kinetic studies of HIV-1 and HIV-2 envelope glycoprotein-mediated fusion

Journal Article · Mon Dec 04 00:00:00 EST 2006 · Retrovirology · OSTI ID:1368229

Gallo, Stephen A.; Reeves, Jacqueline D.; Garg, Himanshu; +3 more

Cryo-EM structures of HIV-1 trimer bound to CD4-mimetics BNM-III-170 and M48U1 adopt a CD4-bound open conformation

Journal Article · Mon Mar 29 00:00:00 EDT 2021 · Nature Communications · OSTI ID:1368229

Jette, Claudia A.; Barnes, Christopher O.; Kirk, Sharon M.; +3 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HIV-1
Membrane fusion
Viral entry
Viral structure
Microbial mutation
CD coreceptors
Point mutation
Cell fusion

Title: Receptor Activation of HIV-1 Env Leads to Asymmetric Exposure of the gp41 Trimer

Citation Formats

References (90)

Cited By (8)

Similar Records

Related Subjects