scholarly journals Structure of HIV-1 Capsid Assemblies by Cryo-electron Microscopy and Iterative Helical Real-space Reconstruction

10.3791/3041 ◽  
2011 ◽  
Author(s):  
Xin Meng ◽  
Gongpu Zhao ◽  
Peijun Zhang
Keyword(s):  
Electron Microscopy ◽  
Real Space ◽  
Cryo Electron Microscopy ◽  
Hiv 1

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 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.

scholarly journals Macromolecular refinement of X-ray and cryo-electron microscopy structures with Phenix / OPLS3e for improved structure and ligand quality

2020 ◽  
Author(s):  
Gydo C.P. van Zundert ◽  
Nigel W. Moriarty ◽  
Oleg V. Sobolev ◽  
Paul D. Adams ◽  
Kenneth W. Borrelli
Keyword(s):  
Electron Microscopy ◽  
Force Field ◽  
Binding Free Energy ◽  
Structure Refinement ◽  
Real Space ◽  
Free Energy Calculations ◽  
Ligand Docking ◽  
Structure Quality ◽  
X Ray ◽  
Cryo Electron Microscopy

AbstractAccurate macromolecular structure refinement is of paramount importance in structure based drug discovery as it provides a gateway to using ligand binding free energy calculations and ligand docking techniques. When dealing with high-resolution data, a simple restraint model may be preferred when the data is able to guide atom parameters to an unambiguous location. However, at lower resolution, the additional information contained in a complex force field may aid in refinement by avoiding implausible structures permitted by the simpler restraints. With the advent of the resolution revolution in cryo-electron microscopy, low resolution refinement is common, and likewise increases the need for a reliable force field. Here we report on the incorporation of the OPLS3e force field with the VSGB2.1 solvation model in the widely used structure determination package Phenix. The implementation is versatile and can be used in both reciprocal and real space refinement, alleviating the need for manually creating accurate ligand restraint dictionaries in the form of CIF files. Our results show significantly improved structure quality at lower resolution for X-ray refinement with reduced ligand strain, while showing only a slight increase in Rfree. For real space refinement of cryo-EM based structures, we find comparable quality structures, goodness-of-fit and reduced ligand strain. In addition, we explicitly show how structure quality is related to the map-model cross correlation as a function of data weight, and how it can be an insightful tool for detecting both over- and underfitting, especially when coupled with ligand energies. Further, we have compiled a user-friendly start-to-end script for refining structures with Phenix/OPLS3e, which is available starting with the Schrödinger 2020-3 distribution.

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