scholarly journals Prefusion structure of trimeric HIV-1 envelope glycoprotein determined by cryo-electron microscopy

2013 ◽  
Vol 20 (12) ◽  
pp. 1352-1357 ◽  
Author(s):  
Alberto Bartesaghi ◽  
Alan Merk ◽  
Mario J Borgnia ◽  
Jacqueline L S Milne ◽  
Sriram Subramaniam
Keyword(s):  
Electron Microscopy ◽  
Envelope Glycoprotein ◽  
Cryo Electron Microscopy ◽  
Hiv 1

scholarly journals Networks of HIV-1 envelope glycans maintain antibody epitopes in the face of glycan additions and deletions

2020 ◽  
Author(s):  
Gemma E. Seabright ◽  
Christopher A. Cottrell ◽  
Marit J. van Gils ◽  
Alessio D’addabbo ◽  
David J. Harvey ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Neutralizing Antibodies ◽  
Broadly Neutralizing Antibodies ◽  
Site Specific ◽  
Glycan Analysis ◽  
Cryo Electron Microscopy ◽  
Immunogen Design ◽  
The Face ◽  
Antibody Epitopes ◽  
Hiv 1

SUMMARYNumerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the hierarchy of importance of glycans in the formation of the 2G12 bnAb epitope, and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.

scholarly journals Cryo-electron microscopy reveals ordered domains in the immature HIV-1 particle

1997 ◽  
Vol 7 (10) ◽  
pp. 729-738 ◽  
Author(s):  
Stephen D. Fuller ◽  
Thomas Wilk ◽  
Brent E. Gowen ◽  
Hans-Georg Kräusslich ◽  
Volker M. Vogt
Keyword(s):  
Electron Microscopy ◽  
Cryo Electron Microscopy ◽  
Hiv 1

scholarly journals Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics

Nature ◽  
2013 ◽  
Vol 497 (7451) ◽  
pp. 643-646 ◽  
Author(s):  
Gongpu Zhao ◽  
Juan R. Perilla ◽  
Ernest L. Yufenyuy ◽  
Xin Meng ◽  
Bo Chen ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Molecular Dynamics ◽  
Cryo Electron Microscopy ◽  
Hiv 1

scholarly journals Comparison of Uncleaved and Mature Human Immunodeficiency Virus Membrane Envelope Glycoprotein Trimers

2018 ◽  
Vol 92 (12) ◽  
Author(s):  
Luis R. Castillo-Menendez ◽  
Kristen Witt ◽  
Nicole Espy ◽  
Amy Princiotto ◽  
Navid Madani ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Human Immunodeficiency Virus ◽  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Hydrodynamic Radius ◽  
Negative Stain ◽  
Immunodeficiency Virus ◽  
Negative Stain Electron Microscopy ◽  
Hiv 1

ABSTRACTThe mature envelope glycoprotein (Env) spike on the surfaces of human immunodeficiency virus type 1 (HIV-1)-infected cells and virions is derived from proteolytic cleavage of a trimeric gp160 glycoprotein precursor. In these studies, we compared the conformations of cleaved and uncleaved membrane Envs with truncated cytoplasmic tails to those of stabilized soluble gp140 SOSIP.664 Env trimers. Deletion of the gp41 cytoplasmic tail did not significantly affect the sensitivity of viruses with the HIV-1AD8Env to inhibition by antibodies or a CD4-mimetic compound. After glutaraldehyde fixation and purification from membranes, a cleaved Env exhibited a hydrodynamic radius of ∼10 nm and an antibody-binding profile largely consistent with that expected based on virus neutralization sensitivity. The purified cleaved Env trimers exhibited a hollow architecture with a central void near the trimer axis. Uncleaved Env, cross-linked and purified in parallel, exhibited a hydrodynamic radius similar to that of the cleaved Env. However, the uncleaved Env was recognized by poorly neutralizing antibodies and appeared by negative-stain electron microscopy to sample multiple conformations. Compared with membrane Envs, stabilized soluble gp140 SOSIP.664 Env trimers appear to be more compact, as reflected in their smaller hydrodynamic radii and negative-stain electron microscopy structures. The antigenic features of the soluble gp140 SOSIP.664 Env trimers differed from those of the cleaved membrane Env, particularly in gp120 V3 and some CD4-binding-site epitopes. Thus, proteolytic maturation allows the membrane-anchored Env to achieve a conformation that retains functional metastability but masks epitopes for poorly neutralizing antibodies.IMPORTANCEThe entry of human immunodeficiency virus type 1 (HIV-1) into host cells is mediated by the envelope glycoprotein (Env) spike on the surface of the virus. Host antibodies elicited during natural HIV-1 infection or by vaccination can potentially recognize the Env spike and block HIV-1 infection. However, the changing shape of the HIV-1 Env spike protects the virus from antibody binding. Understanding the shapes of natural and man-made preparations of HIV-1 Envs will assist the development of effective vaccines against the virus. Here, we evaluate the effects of several Env modifications commonly used to produce Env preparations for vaccine studies and the determination of structure. We found that the cleavage of the HIV-1 Env precursor helps Env to assume its natural shape, which resists the binding of many commonly elicited antibodies. Stabilized soluble Envs exhibit more compact shapes but expose some Env elements differently than the natural Env.

scholarly journals Cryo-electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly

2014 ◽  
Vol 111 (22) ◽  
pp. 8233-8238 ◽  
Author(s):  
T. A. M. Bharat ◽  
L. R. Castillo Menendez ◽  
W. J. H. Hagen ◽  
V. Lux ◽  
S. Igonet ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Virus Assembly ◽  
Cryo Electron Microscopy ◽  
Immature Virus ◽  
Hiv 1 ◽  
Tubular Arrays

scholarly journals A supramolecular assembly mediates lentiviral DNA integration

Science ◽  
2017 ◽  
Vol 355 (6320) ◽  
pp. 93-95 ◽  
Author(s):  
Allison Ballandras-Colas ◽  
Daniel P. Maskell ◽  
Erik Serrao ◽  
Julia Locke ◽  
Paolo Swuec ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Supramolecular Assembly ◽  
Structural Data ◽  
Higher Order ◽  
Viral Dna ◽  
Dna Integration ◽  
Cryo Electron Microscopy ◽  
Nucleoprotein Complex ◽  
Retroviral Integrase ◽  
Hiv 1

Retroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo–electron microscopy, we now visualize the functional maedi-visna lentivirus intasome at 4.9 angstrom resolution. The intasome comprises a homo-hexadecamer of IN with a tetramer-of-tetramers architecture featuring eight structurally distinct types of IN protomers supporting two catalytically competent subunits. The conserved intasomal core, previously observed in simpler retroviral systems, is formed between two IN tetramers, with a pair of C-terminal domains from flanking tetramers completing the synaptic interface. Our results explain how HIV-1 IN, which self-associates into higher-order multimers, can form a functional intasome, reconcile the bulk of early HIV-1 IN biochemical and structural data, and provide a lentiviral platform for design of HIV-1 IN inhibitors.

scholarly journals PRISM-EM: template interface-based modelling of multi-protein complexes guided by cryo-electron microscopy density maps

2016 ◽  
Vol 72 (10) ◽  
pp. 1137-1148 ◽  
Author(s):  
Guray Kuzu ◽  
Ozlem Keskin ◽  
Ruth Nussinov ◽  
Attila Gursoy
Keyword(s):  
Electron Microscopy ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Protein Assemblies ◽  
New Approach ◽  
Cellular Processes ◽  
Cryo Electron Microscopy ◽  
Density Maps ◽  
Crystallographic Structures ◽  
Hiv 1

The structures of protein assemblies are important for elucidating cellular processes at the molecular level. Three-dimensional electron microscopy (3DEM) is a powerful method to identify the structures of assemblies, especially those that are challenging to study by crystallography. Here, a new approach, PRISM-EM, is reported to computationally generate plausible structural models using a procedure that combines crystallographic structures and density maps obtained from 3DEM. The predictions are validated against seven available structurally different crystallographic complexes. The models display mean deviations in the backbone of <5 Å. PRISM-EM was further tested on different benchmark sets; the accuracy was evaluated with respect to the structure of the complex, and the correlation with EM density maps and interface predictions were evaluated and compared with those obtained using other methods. PRISM-EM was then used to predict the structure of the ternary complex of the HIV-1 envelope glycoprotein trimer, the ligand CD4 and the neutralizing protein m36.

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