scholarly journals Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

2016 ◽  
Author(s):  
John M A Grime ◽  
James F Dama ◽  
Barbie K Ganser-Pornillos ◽  
Cora L Woodward ◽  
Grant J Jensen ◽  
...  
Keyword(s):  
Self Assembly ◽  
Coarse Grained ◽  
Capsid Assembly ◽  
Molecular Crowding ◽  
Local Conditions ◽  
Conformational Variability ◽  
Multi Stage ◽  
Capsid Shell ◽  
Coarse Grained Simulations ◽  
Hiv 1

The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies.

scholarly journals Self-Assembly of Epstein-Barr Virus Capsids

2009 ◽  
Vol 83 (8) ◽  
pp. 3877-3890 ◽  
Author(s):  
Brandon W. Henson ◽  
Edward M. Perkins ◽  
Jonathan E. Cothran ◽  
Prashant Desai
Keyword(s):  
Amino Acids ◽  
Capsid Protein ◽  
Self Assembly ◽  
Epstein Barr Virus ◽  
Major Capsid Protein ◽  
Mutational Analysis ◽  
Capsid Assembly ◽  
Barr Virus ◽  
Capsid Shell ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV), a member of the Gammaherpesvirus family, primarily infects B lymphocytes and is responsible for a number of lymphoproliferative diseases. The molecular genetics of the assembly pathway and high-resolution structural analysis of the capsid have not been determined for this lymphocryptovirus. As a first step in studying EBV capsid assembly, the baculovirus expression vector (BEV) system was used to express the capsid shell proteins BcLF1 (major capsid protein), BORF1 (triplex protein), BDLF1 (triplex protein), and BFRF3 (small capsid protein); the internal scaffold protein, BdRF1; and the maturational protease (BVRF2). Coinfection of insect cells with the six viruses expressing these proteins resulted in the production of closed capsid structures as judged by electron microscopy and sedimentation methods. Therefore, as shown for other herpesviruses, only six proteins are required for EBV capsid assembly. Furthermore, the small capsid protein of EBV (BFRF3), like that of Kaposi's sarcoma-associated herpesvirus, was found to be required for assembly of a stable structure. Localization of the small capsid protein to nuclear assembly sites required both the major capsid (BcLF1) and scaffold proteins (BdRF1) but not the triplex proteins. Mutational analysis of BFRF3 showed that the N-terminal half (amino acids 1 to 88) of this polypeptide is required and sufficient for capsid assembly. A region spanning amino acids 65 to 88 is required for the concentration of BFRF3 at a subnuclear site and the N-terminal 65 amino acids contain the sequences required for interaction with major capsid protein. These studies have identified the multifunctional role of the gammaherpesvirus small capsid proteins.

scholarly journals Shape selection and mis-assembly in viral capsid formation by elastic frustration

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Carlos I Mendoza ◽  
David Reguera
Keyword(s):  
Self Assembly ◽  
Viral Infections ◽  
Coarse Grained ◽  
Energetic Cost ◽  
Mechanical Resistance ◽  
Elastic Stresses ◽  
Shape Selection ◽  
Spherical Structures ◽  
Coarse Grained Simulations ◽  
Successful Replication

The successful assembly of a closed protein shell (or capsid) is a key step in the replication of viruses and in the production of artificial viral cages for bio/nanotechnological applications. During self-assembly, the favorable binding energy competes with the energetic cost of the growing edge and the elastic stresses generated due to the curvature of the capsid. As a result, incomplete structures such as open caps, cylindrical or ribbon-shaped shells may emerge, preventing the successful replication of viruses. Using elasticity theory and coarse-grained simulations, we analyze the conditions required for these processes to occur and their significance for empty virus self-assembly. We find that the outcome of the assembly can be recast into a universal phase diagram showing that viruses with high mechanical resistance cannot be self-assembled directly as spherical structures. The results of our study justify the need of a maturation step and suggest promising routes to hinder viral infections by inducing mis-assembly.

scholarly journals The influence of arm composition on the self-assembly of low-functionality telechelic star polymers in dilute solutions

2020 ◽  
Author(s):  
Esmaeel Moghimi ◽  
Iurii Chubak ◽  
Dimitra Founta ◽  
Konstantinos Ntetsikas ◽  
George Polymeropoulos ◽  
...  
Keyword(s):  
Self Assembly ◽  
Dynamic Properties ◽  
Star Polymers ◽  
Coarse Grained ◽  
Dilute Solutions ◽  
Solvent Quality ◽  
Physical Experiments ◽  
Coarse Grained Simulations ◽  
Two Populations

Abstract We combine synthesis, physical experiments, and computer simulations to investigate self-assembly patterns of low-functionality telechelic star polymers (TSPs) in dilute solutions. In particular, in this work, we focus on the effect of the arm composition and length on the static and dynamic properties of TSPs, whose terminal blocks are subject to worsening solvent quality upon reducing the temperature. We find two populations, single stars and clusters, that emerge upon worsening the solvent quality of the outer block. For both types of populations, their spatial extent decreases with temperature, with the specific details (such as temperature at which the minimal size is reached) depending on the coupling between inter- and intra-molecular associations as well as their strength. The experimental results are in very good qualitative agreement with coarse-grained simulations, which offer insights into the mechanism of thermoresponsive behavior of this class of materials.

scholarly journals Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
John M. A. Grime ◽  
James F. Dama ◽  
Barbie K. Ganser-Pornillos ◽  
Cora L. Woodward ◽  
Grant J. Jensen ◽  
...  
Keyword(s):  
Self Assembly ◽  
Coarse Grained ◽  
Key Features ◽  
Hiv 1

scholarly journals Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane

2017 ◽  
Vol 114 (47) ◽  
pp. E10056-E10065 ◽  
Author(s):  
Alexander J. Pak ◽  
John M. A. Grime ◽  
Prabuddha Sengupta ◽  
Antony K. Chen ◽  
Aleksander E. P. Durumeric ◽  
...  
Keyword(s):  
Self Assembly ◽  
Structural Data ◽  
Single Particle Tracking ◽  
Viral Rna ◽  
Coarse Grained ◽  
Amino Terminal ◽  
Gag Polyprotein ◽  
Amino Terminal Domain ◽  
Hiv 1 ◽  
Simple Network

The packaging and budding of Gag polyprotein and viral RNA is a critical step in the HIV-1 life cycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization process, especially in the presence of RNA and the cell membrane, have remained unclear. In this work, we investigate the mechanisms that work in concert between the polyproteins, RNA, and membrane to promote immature lattice growth. We develop a coarse-grained (CG) computational model that is derived from subnanometer resolution structural data. Our simulations recapitulate contiguous and hexameric lattice assembly driven only by weak anisotropic attractions at the helical CA–SP1 junction. Importantly, analysis from CG and single-particle tracking photoactivated localization (spt-PALM) trajectories indicates that viral RNA and the membrane are critical constituents that actively promote Gag multimerization through scaffolding, while overexpression of short competitor RNA can suppress assembly. We also find that the CA amino-terminal domain imparts intrinsic curvature to the Gag lattice. As a consequence, immature lattice growth appears to be coupled to the dynamics of spontaneous membrane deformation. Our findings elucidate a simple network of interactions that regulate the early stages of HIV-1 assembly and budding.

scholarly journals Coarse-Grained Simulations of the HIV-1 Matrix Protein Anchoring: Revisiting Its Assembly on Membrane Domains

2014 ◽  
Vol 106 (3) ◽  
pp. 577-585 ◽  
Author(s):  
Landry Charlier ◽  
Maxime Louet ◽  
Laurent Chaloin ◽  
Patrick Fuchs ◽  
Jean Martinez ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Coarse Grained ◽  
Membrane Domains ◽  
Coarse Grained Simulations ◽  
Hiv 1
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