scholarly journals The Roles of Electrostatic Interactions in Capsid Assembly Mechanisms of Giant Viruses

2019 ◽  
Vol 20 (8) ◽  
pp. 1876 ◽  
Author(s):  
Yuejiao Xian ◽  
Chitra B. Karki ◽  
Sebastian Miki Silva ◽  
Lin Li ◽  
Chuan Xiao
Keyword(s):  
Self Assembly ◽  
Electrostatic Interactions ◽  
Virus Assembly ◽  
Binding Mode ◽  
Giant Virus ◽  
Capsid Assembly ◽  
Fold Axis ◽  
Binding Modes ◽  
Dna Viruses ◽  
Giant Viruses

In the last three decades, many giant DNA viruses have been discovered. Giant viruses present a unique and essential research frontier for studies of self-assembly and regulation of supramolecular assemblies. The question on how these giant DNA viruses assemble thousands of proteins so accurately to form their protein shells, the capsids, remains largely unanswered. Revealing the mechanisms of giant virus assembly will help to discover the mysteries of many self-assembly biology problems. Paramecium bursaria Chlorella virus-1 (PBCV-1) is one of the most intensively studied giant viruses. Here, we implemented a multi-scale approach to investigate the interactions among PBCV-1 capsid building units called capsomers. Three binding modes with different strengths are found between capsomers around the relatively flat area of the virion surface at the icosahedral 2-fold axis. Furthermore, a capsomer structure manipulation package is developed to simulate the capsid assembly process. Using these tools, binding forces among capsomers were investigated and binding funnels were observed that were consistent with the final assembled capsid. In addition, total binding free energies of each binding mode were calculated. The results helped to explain previous experimental observations. Results and tools generated in this work established an initial computational approach to answer current unresolved questions regarding giant virus assembly mechanisms. Results will pave the way for studying more complicated process in other biomolecular structures.

scholarly journals First evidence of host range expansion in virophages and its potential impact on giant viruses and host cells

2019 ◽  
Author(s):  
Said Mougari ◽  
Nisrine Chelkha ◽  
Dehia Sahmi-Bounsiar ◽  
Fabrizio Di Pinto ◽  
Philippe Colson ◽  
...  
Keyword(s):  
Host Range ◽  
Range Expansion ◽  
Virus Production ◽  
Host Cells ◽  
Giant Virus ◽  
Dna Viruses ◽  
Host Range Expansion ◽  
Parasitic Lifestyle ◽  
Giant Viruses ◽  
Viral Host Range

AbstractVirophages are satellite-like double stranded DNA viruses whose replication requires the presence of two biological entities, a giant virus and a protist. In this report, we present the first evidence of host range expansion in a virophage. We demonstrated that the Guarani virophage was able to spontaneously expand its viral host range to replicate with two novel giant viruses that were previously nonpermissive to this virophage. We were able to characterize a potential genetic determinant of this cross-species infection. We then highlighted the relevant impact of this host adaptation on giant viruses and protists by demonstrating that coinfection with the mutant virophage abolishes giant virus production and rescues the host cell population from lysis. The results of our study help to elucidate the parasitic lifestyle of virophages and their interactions with giant viruses and protists.

DNA Photocleavage and Binding Modes of Methylene Violet 3RAX and its Derivatives: Effect of Functional Groups

2017 ◽  
Vol 70 (7) ◽  
pp. 830 ◽  
Author(s):  
Ke Yang ◽  
Xiong Zhang ◽  
Fang Yang ◽  
Fengshou Wu ◽  
Xiulan Zhang ◽  
...  
Keyword(s):  
Singlet Oxygen ◽  
Electrostatic Interactions ◽  
1H Nmr Spectroscopy ◽  
Binding Mode ◽  
Binding Modes ◽  
Oxygen Production ◽  
Groove Binding ◽  
Dna Photocleavage ◽  
Intercalative Mode ◽  
Methylene Violet

With 4′-amino-N,N-diethylaniline and aniline as starting materials, methylene violet 3RAX 1 and its derivatives 2–5 were synthesised. The five compounds were characterised by IR, UV-vis, and 1H NMR spectroscopy and mass spectrometry. The binding mode between the synthesised compounds and DNA were investigated. The results show that both compounds 1 and 5 bind to DNA by an intercalative mode, while compounds 2–4 interact with DNA through a mixed binding mode involving groove binding and electrostatic interactions. The photocleavage ability of the five compounds to DNA were calculated to be 38, 40, 30, 20, and 13 %, respectively, when their concentration was adjusted to 400 μM. The singlet oxygen production of compounds measured by the 1,3-diphenylisobenzofuran method was consistent with the trend of DNA photocleavage ability. The DNA studies suggest that the binding mode between methylene violet 3RAX and DNA, the ability of methylene violet 3RAX to generate singlet oxygen, and the DNA photocleavage activity could be adjusted through modification of the amino group on methylene violet 3RAX.

scholarly journals A capsid with a twist: Assembly mechanism of the pleomorphic immature poxvirus scaffold

2021 ◽  
Author(s):  
Matthias Wolf ◽  
Jae-Kyung Hyun ◽  
Hideyuki Matsunami ◽  
Tae Gyun Kim
Keyword(s):  
Self Assembly ◽  
Electrostatic Interactions ◽  
Dna Viruses ◽  
Assembly Mechanism ◽  
Single Protein ◽  
Immature Virion ◽  
Nucleocytoplasmic Large Dna Viruses ◽  
Continuous Curvature ◽  
Α Helix

Abstract In Vaccinia virus (VACV), the prototype poxvirus, scaffold protein D13 forms a honeycomb-like lattice on the viral membrane that results in formation of the pleomorphic immature virion (IV). The structure of D13 is similar to those of major capsid proteins that readily form icosahedral capsids in nucleocytoplasmic large DNA viruses (NCLDVs). However, the detailed assembly mechanism of the non-icosahedral poxvirus scaffold has never been understood. Here we show the cryo-EM structures of D13 trimer and scaffold intermediates produced in vitro. The structures reveal that the short N-terminal α-helix is critical for initiation of D13 self-assembly. The continuous curvature of the IV is mediated by electrostatic interactions that induce torsion between trimers. The assembly mechanism explains the semi-ordered capsid-like arrangement of D13 that is distinct from icosahedral NCLDVs. Our structures explain how a single protein can self-assemble into different capsid morphologies, and represents a local exception to the universal Caspar-Klug theory of quasi-equivalence.

scholarly journals Advantages and Limits of Metagenomic Assembly and Binning of a Giant Virus

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Frederik Schulz ◽  
Julien Andreani ◽  
Rania Francis ◽  
Hadjer Boudjemaa ◽  
Jacques Yaacoub Bou Khalil ◽  
...  
Keyword(s):  
Sequence Data ◽  
Giant Virus ◽  
Dna Viruses ◽  
Successful Recovery ◽  
Metagenome Assembly ◽  
Giant Viruses ◽  
Nucleocytoplasmic Large Dna Viruses ◽  
Metagenomic Assembly ◽  
Virus Genomes ◽  
Coding Potential

ABSTRACT Giant viruses have large genomes, often within the size range of cellular organisms. This distinguishes them from most other viruses and demands additional effort for the successful recovery of their genomes from environmental sequence data. Here, we tested the performance of genome-resolved metagenomics on a recently isolated giant virus, Fadolivirus, by spiking it into an environmental sample from which two other giant viruses were isolated. At high spike-in levels, metagenome assembly and binning led to the successful genomic recovery of Fadolivirus from the sample. A complementary survey of the major capsid protein indicated the presence of other giant viruses in the sample matrix but did not detect the two isolated from this sample. Our results indicate that genome-resolved metagenomics is a valid approach for the recovery of near-complete giant virus genomes given that sufficient clonal particles are present. However, our data also underline that a vast majority of giant viruses remain currently undetected, even in an era of terabase-scale metagenomics. IMPORTANCE The discovery of large and giant nucleocytoplasmic large DNA viruses (NCLDV) with genomes in the megabase range and equipped with a wide variety of features typically associated with cellular organisms was one of the most unexpected, intriguing, and spectacular breakthroughs in virology. Recent studies suggest that these viruses are highly abundant in the oceans, freshwater, and soil, impact the biology and ecology of their eukaryotic hosts, and ultimately affect global nutrient cycles. Genome-resolved metagenomics is becoming an increasingly popular tool to assess the diversity and coding potential of giant viruses, but this approach is currently lacking validation.

scholarly journals In-depth study of Mollivirus sibericum, a new 30,000-y-old giant virus infecting Acanthamoeba

2015 ◽  
Vol 112 (38) ◽  
pp. E5327-E5335 ◽  
Author(s):  
Matthieu Legendre ◽  
Audrey Lartigue ◽  
Lionel Bertaux ◽  
Sandra Jeudy ◽  
Julia Bartoli ◽  
...  
Keyword(s):  
Global Warming ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Ribosomal Proteins ◽  
Acanthamoeba Castellanii ◽  
Giant Virus ◽  
Metagenomic Analysis ◽  
Dna Viruses ◽  
Depth Study ◽  
Giant Viruses

Acanthamoeba species are infected by the largest known DNA viruses. These include icosahedral Mimiviruses, amphora-shaped Pandoraviruses, and Pithovirus sibericum, the latter one isolated from 30,000-y-old permafrost. Mollivirus sibericum, a fourth type of giant virus, was isolated from the same permafrost sample. Its approximately spherical virion (0.6-µm diameter) encloses a 651-kb GC-rich genome encoding 523 proteins of which 64% are ORFans; 16% have their closest homolog in Pandoraviruses and 10% in Acanthamoeba castellanii probably through horizontal gene transfer. The Mollivirus nucleocytoplasmic replication cycle was analyzed using a combination of “omic” approaches that revealed how the virus highjacks its host machinery to actively replicate. Surprisingly, the host’s ribosomal proteins are packaged in the virion. Metagenomic analysis of the permafrost sample uncovered the presence of both viruses, yet in very low amount. The fact that two different viruses retain their infectivity in prehistorical permafrost layers should be of concern in a context of global warming. Giant viruses’ diversity remains to be fully explored.

scholarly journals A phylogenomic framework for charting the diversity and evolution of giant viruses

PLoS Biology ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. e3001430
Author(s):  
Frank O. Aylward ◽  
Mohammad Moniruzzaman ◽  
Anh D. Ha ◽  
Eugene V. Koonin
Keyword(s):  
Giant Virus ◽  
Phylogenomic Analysis ◽  
Environmental Distribution ◽  
Dna Viruses ◽  
Giant Viruses ◽  
Taxonomic Framework

Large DNA viruses of the phylum Nucleocytoviricota have recently emerged as important members of ecosystems around the globe that challenge traditional views of viral complexity. Numerous members of this phylum that cannot be classified within established families have recently been reported, and there is presently a strong need for a robust phylogenomic and taxonomic framework for these viruses. Here, we report a comprehensive phylogenomic analysis of the Nucleocytoviricota, present a set of giant virus orthologous groups (GVOGs) together with a benchmarked reference phylogeny, and delineate a hierarchical taxonomy within this phylum. We show that the majority of Nucleocytoviricota diversity can be partitioned into 6 orders, 32 families, and 344 genera, substantially expanding the number of currently recognized taxonomic ranks for these viruses. We integrate our results within a taxonomy that has been adopted for all viruses to establish a unifying framework for the study of Nucleocytoviricota diversity, evolution, and environmental distribution.

scholarly journals Using computational approaches to study dengue virus capsid assembly

2019 ◽  
Vol 7 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Gicela G Saucedo Salas ◽  
Alan E Lopez Hernandez ◽  
Jiadi He ◽  
Chitra Karki ◽  
Yixin Xie ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Binding Mode ◽  
Viral Capsid ◽  
Capsid Assembly ◽  
Salt Bridges ◽  
Binding Modes ◽  
Mode Iii ◽  
Virus Capsid ◽  
Computational Approaches ◽  
M Proteins

AbstractDengue viral capsid plays a significant role in viral life cycle of dengue, especially in vial genome protection and virus-cell fusion. Revealing mechanisms of the viral capsid protein assembly may lead to the discovery of anti-viral drugs that inhibit the assembly of the viral capsid. The E and M-proteins are arranged into heterotetramers, which consists of two copies of E and M-protein. The heterotetramers are assembled into a highly ordered capsid. While many investigations of the interactions between E and M-proteins have been performed, there are very few studies on the interactions between the heterotetramers and their roles in capsid assembly. Utilizing a series of computational approaches, this study focuses on the assembly mechanism of the heterotetramers. Our electrostatic analyses lead to the identification of four binding modes between each two dengue heterotetramers that repeat periodically throughout the virus capsid. Among these four binding modes, heterotetramers in binding modes I, II and IV are attractive. But in the binding mode III the heterotetramers repel each other, making mode III a suitable target for drug design. Furthermore, MD simulations were performed following by salt bridges analysis. This study demonstrates that using computational approaches is a promising direction to study the dengue virus.

Binding Modes of Ligands Using Enhanced Sampling (BLUES): Rapid Decorrelation of Ligand Binding Modes Using Nonequilibrium Candidate Monte Carlo

2017 ◽  
Author(s):  
Samuel Gill ◽  
Nathan M. Lim ◽  
Patrick Grinaway ◽  
Ariën S. Rustenburg ◽  
Josh Fass ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Ligand Binding ◽  
Binding Mode ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Binding Modes ◽  
Enhanced Sampling ◽  
Recent Success ◽  
Multiple Binding ◽  
Proper Sampling

<div>Accurately predicting protein-ligand binding is a major goal in computational chemistry, but even the prediction of ligand binding modes in proteins poses major challenges. Here, we focus on solving the binding mode prediction problem for rigid fragments. That is, we focus on computing the dominant placement, conformation, and orientations of a relatively rigid, fragment-like ligand in a receptor, and the populations of the multiple binding modes which may be relevant. This problem is important in its own right, but is even more timely given the recent success of alchemical free energy calculations. Alchemical calculations are increasingly used to predict binding free energies of ligands to receptors. However, the accuracy of these calculations is dependent on proper sampling of the relevant ligand binding modes. Unfortunately, ligand binding modes may often be uncertain, hard to predict, and/or slow to interconvert on simulation timescales, so proper sampling with current techniques can require prohibitively long simulations. We need new methods which dramatically improve sampling of ligand binding modes. Here, we develop and apply a nonequilibrium candidate Monte Carlo (NCMC) method to improve sampling of ligand binding modes.</div><div><br></div><div>In this technique the ligand is rotated and subsequently allowed to relax in its new position through alchemical perturbation before accepting or rejecting the rotation and relaxation as a nonequilibrium Monte Carlo move. When applied to a T4 lysozyme model binding system, this NCMC method shows over two orders of magnitude improvement in binding mode sampling efficiency compared to a brute force molecular dynamics simulation. This is a first step towards applying this methodology to pharmaceutically relevant binding of fragments and, eventually, drug-like molecules. We are making this approach available via our new Binding Modes of Ligands using Enhanced Sampling (BLUES) package which is freely available on GitHub.</div>

Binding Modes of Ligands Using Enhanced Sampling (BLUES): Rapid Decorrelation of Ligand Binding Modes Using Nonequilibrium Candidate Monte Carlo

2018 ◽  
Author(s):  
Samuel Gill ◽  
Nathan M. Lim ◽  
Patrick Grinaway ◽  
Ariën S. Rustenburg ◽  
Josh Fass ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Ligand Binding ◽  
Binding Mode ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Binding Modes ◽  
Enhanced Sampling ◽  
Recent Success ◽  
Multiple Binding ◽  
Proper Sampling

<div>Accurately predicting protein-ligand binding is a major goal in computational chemistry, but even the prediction of ligand binding modes in proteins poses major challenges. Here, we focus on solving the binding mode prediction problem for rigid fragments. That is, we focus on computing the dominant placement, conformation, and orientations of a relatively rigid, fragment-like ligand in a receptor, and the populations of the multiple binding modes which may be relevant. This problem is important in its own right, but is even more timely given the recent success of alchemical free energy calculations. Alchemical calculations are increasingly used to predict binding free energies of ligands to receptors. However, the accuracy of these calculations is dependent on proper sampling of the relevant ligand binding modes. Unfortunately, ligand binding modes may often be uncertain, hard to predict, and/or slow to interconvert on simulation timescales, so proper sampling with current techniques can require prohibitively long simulations. We need new methods which dramatically improve sampling of ligand binding modes. Here, we develop and apply a nonequilibrium candidate Monte Carlo (NCMC) method to improve sampling of ligand binding modes.</div><div><br></div><div>In this technique the ligand is rotated and subsequently allowed to relax in its new position through alchemical perturbation before accepting or rejecting the rotation and relaxation as a nonequilibrium Monte Carlo move. When applied to a T4 lysozyme model binding system, this NCMC method shows over two orders of magnitude improvement in binding mode sampling efficiency compared to a brute force molecular dynamics simulation. This is a first step towards applying this methodology to pharmaceutically relevant binding of fragments and, eventually, drug-like molecules. We are making this approach available via our new Binding Modes of Ligands using Enhanced Sampling (BLUES) package which is freely available on GitHub.</div>

In situ Time-Resolved Small-Angle X-ray Scattering Reveals the Formation Kinetics of Polyelectrolyte Complex Micelles

2019 ◽  
Author(s):  
Hao Wu ◽  
Jeffrey Ting ◽  
Siqi Meng ◽  
Matthew Tirrell
Keyword(s):  
Small Angle ◽  
Self Assembly ◽  
Electrostatic Interactions ◽  
Polyelectrolyte Complex ◽  
Time Resolved ◽  
X Ray ◽  
X Ray Scattering ◽  
Kinetics Of ◽  
Ray Scattering

We have directly observed the <i>in situ</i> self-assembly kinetics of polyelectrolyte complex (PEC) micelles by synchrotron time-resolved small-angle X-ray scattering, equipped with a stopped-flow device that provides millisecond temporal resolution. This work has elucidated one general kinetic pathway for the process of PEC micelle formation, which provides useful physical insights for increasing our fundamental understanding of complexation and self-assembly dynamics driven by electrostatic interactions that occur on ultrafast timescales.

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