scholarly journals Functional Dissection of the Major Structural Protein of Bluetongue Virus: Identification of Key Residues within VP7 Essential for Capsid Assembly

2000 ◽  
Vol 74 (18) ◽  
pp. 8658-8669 ◽  
Author(s):  
Chang-Kwang Limn ◽  
Norbert Staeuber ◽  
Katherine Monastyrskaya ◽  
Patrice Gouet ◽  
Polly Roy
Keyword(s):  
Bluetongue Virus ◽  
Cdna Clones ◽  
Structural Protein ◽  
Apparent Effect ◽  
Dynamic Nature ◽  
Virus Identification ◽  
Substitution Mutations ◽  
The Stability ◽  
Key Residues

ABSTRACT A lattice of VP7 trimers forms the surface of the icosahedral bluetongue virus (BTV) core. To investigate the role of VP7 oligomerization in core assembly, a series of residues for substitution were predicted based on crystal structures of BTV type 10 VP7 molecule targeting the monomer-monomer contacts within the trimer. Seven site-specific substitution mutations of VP7 have been created using cDNA clones and were employed to produce seven recombinant baculoviruses. The effects of these mutations on VP7 solubility, ability to trimerize and formation of core-like particles (CLPs) in the presence of the scaffolding VP3 protein, were investigated. Of the seven VP7 mutants examined, three severely affected the stability of CLP, while two other mutants had lesser effect on CLP stability. Only one mutant had no apparent effect on the formation of the stable capsid. One mutant in which the conserved tyrosine at residue 271 (lower domain helix 6) was replaced by arginine formed insoluble aggregates, implying an effect in the folding of the molecule despite the prediction that such a change would be accommodated. All six soluble VP7 mutants were purified, and their ability to trimerize was examined. All mutants, including those that did not form stable CLPs, assembled into stable trimers, implying that single substitution may not be sufficient to perturb the complex monomer-monomer contacts, although subtle changes within the VP7 trimer could destabilize the core. The study highlights some of the key residues that are crucial for BTV core assembly and illustrates how the structure of VP7 in isolation underrepresents the dynamic nature of the assembly process at the biological level.

scholarly journals Multiple Routes of Bluetongue Virus Egress

2020 ◽  
Vol 8 (7) ◽  
pp. 965
Author(s):  
Thomas Labadie ◽  
Edward Sullivan ◽  
Polly Roy
Keyword(s):  
Cell Sorting ◽  
Bluetongue Virus ◽  
Economic Loss ◽  
Structural Protein ◽  
Enveloped Virus ◽  
Main Driver ◽  
Multiple Routes ◽  
Infected Cells ◽  
Virus Egress

Bluetongue virus (BTV) is an arthropod-borne virus infecting livestock. Its frequent emergence in Europe and North America had caused significant agricultural and economic loss. BTV is also of scientific interest as a model to understand the mechanisms underlying non-enveloped virus release from mammalian and insect cells. The BTV particle, which is formed of a complex double-layered capsid, was first considered as a lytic virus that needs to lyse the infected cells for cell to cell transmission. In the last decade, however, a more in-depth focus on the role of the non-structural proteins has led to several examples where BTV particles are also released through different budding mechanisms at the plasma membrane. It is now clear that the non-structural protein NS3 is the main driver of BTV release, via different interactions with both viral and cellular proteins of the cell sorting and exocytosis pathway. In this review, we discuss the most recent advances in the molecular biology of BTV egress and compare the mechanisms that lead to lytic or non-lytic BTV release.

scholarly journals SARS-CoV-2 NSP-12 mutations survey during the pandemic in the world

2021 ◽  
Author(s):  
Sogol Mazhari ◽  
Helia Alavifard ◽  
Karim Rahimian ◽  
Zohreh Karimi ◽  
Mohammadamin Mahmanzar ◽  
...  
Keyword(s):  
Critical Role ◽  
Reference Sequence ◽  
Structural Protein ◽  
Inclusion Criteria ◽  
The World ◽  
Biochemical Studies ◽  
Severity Of The Disease ◽  
The Stability ◽  
Python Programming

Abstract Background SARS-CoV-2 belongs to the beta coronavirus family responsible for coronavirus disease 2019 (COVID-19), a novel severe acute respiratory syndrome pandemic. The infection first emerged in Wuhan, China, and rapidly spread worldwide. The ongoing outbreak has posed an urgent worldwide health threat due to the rapid transmittable potential and high mortality rate. Due to the critical role of none structural protein − 12 (NSP-12) in COVID-19. This study tries to investigate the link between genotype-phenotype NSP-12 variation and the prevalence of this disease. Methods We analyzed approximately 2 million Nsp12 of SARS-CoV-2 protein sequence from January 2020 until June 2021. Python programming language was utilized to preprocess and apply inclusion criteria on FASTA files to prepare a list of suitable samples for clustering samples. NSP-12 regions were aligned to the reference sequence to compare and identify mutation patterns, categorized based on frequency and continent. Results The rate of ‌NSP-12 mutation in divided geographical areas was different. Based on continental studies, the P227L and G671S mutations have multiplied over time and in European and Asian societies in recent months. According to biochemical studies, the occurrence of G671S mutation increases the stability of the protein. Conclusion We concluded that NSP-12 P227L and G671S mutations in SARS-CoV-2 are increased in recent months. Further studies will be required to investigate whether these mutations impact the severity of the disease.

A Statistical Study of Process Variables to Optimize a High Speed Curtain Coater: Part I

TAPPI Journal ◽  
2009 ◽  
Vol 8 (1) ◽  
pp. 20-26 ◽  
Author(s):  
PEEYUSH TRIPATHI ◽  
MARGARET JOYCE ◽  
PAUL D. FLEMING ◽  
MASAHIRO SUGIHARA
Keyword(s):  
Boundary Layer ◽  
Experimental Design ◽  
High Speed ◽  
Statistical Study ◽  
Process Variables ◽  
High Speeds ◽  
The Stability ◽  
Air Removal ◽  
Removal System

Using an experimental design approach, researchers altered process parameters and material prop-erties to stabilize the curtain of a pilot curtain coater at high speeds. Part I of this paper identifies the four significant variables that influence curtain stability. The boundary layer air removal system was critical to the stability of the curtain and base sheet roughness was found to be very important. A shear thinning coating rheology and higher curtain heights improved the curtain stability at high speeds. The sizing of the base sheet affected coverage and cur-tain stability because of its effect on base sheet wettability. The role of surfactant was inconclusive. Part II of this paper will report on further optimization of curtain stability with these four variables using a D-optimal partial-facto-rial design.

The Role of Hydrophobicity in the Stability and pH-Switchability of (RXDX)4 and Coumarin-RXDX Conjugate β-Sheets

2020 ◽  
Author(s):  
Ryan Weber ◽  
Martin McCullagh
Keyword(s):  
Biological Imaging ◽  
Ph Sensing ◽  
Hydrophobic Residue ◽  
Ideal Candidate ◽  
Self Assembling ◽  
Sensing Applications ◽  
Β Sheets ◽  
The Stability ◽  
Dynamics Simulations

<p>pH-switchable, self-assembling materials are of interest in biological imaging and sensing applications. Here we propose that combining the pH-switchability of RXDX (X=Ala, Val, Leu, Ile, Phe) peptides and the optical properties of coumarin creates an ideal candidate for these materials. This suggestion is tested with a thorough set of all-atom molecular dynamics simulations. We first investigate the dependence of pH-switchabiliy on the identity of the hydrophobic residue, X, in the bare (RXDX)<sub>4</sub> systems. Increasing the hydrophobicity stabilizes the fiber which, in turn, reduces the pH-switchabilty of the system. This behavior is found to be somewhat transferable to systems in which a single hydrophobic residue is replaced with a coumarin containing amino acid. In this case, conjugates with X=Ala are found to be unstable and both pHs while conjugates with X=Val, Leu, Ile and Phe are found to form stable β-sheets at least at neutral pH. The (RFDF)<sub>4</sub>-coumarin conjugate is found to have the largest relative entropy value of 0.884 +/- 0.001 between neutral and acidic coumarin ordering distributions. Thus, we posit that coumarin-(RFDF)<sub>4</sub> containing peptide sequences are ideal candidates for pH-sensing bioelectronic materials.</p>

Metal-Metal Cooperative Bond Activation by Heterobimetallic Alkyl, Aryl, and Acetylide PtII/CuI Complexes

2020 ◽  
Author(s):  
Shubham Deolka ◽  
Orestes Rivada Wheelaghan ◽  
Sandra Aristizábal ◽  
Robert Fayzullin ◽  
Shrinwantu Pal ◽  
...  
Keyword(s):  
Alkyl Group ◽  
Bond Activation ◽  
Bond Cleavage ◽  
Terminal Alkyne ◽  
Alkyl Aryl ◽  
Metal Metal ◽  
The Stability ◽  
Selective Formation ◽  
Organoplatinum Compounds

We report selective formation of heterobimetallic PtII/CuI complexes that demonstrate how facile bond activation processes can be achieved by altering reactivity of common organoplatinum compounds through their interaction with another metal center. The interaction of the Cu center with Pt center and with a Pt-bound alkyl group increases the stability of PtMe2 towards undesired rollover cyclometalation. The presence of the CuI center also enables facile transmetalation from electron-deficient tetraarylborate [B(ArF)4]- anion and mild C-H bond cleavage of a terminal alkyne, which was not observed in the absence of an electrophilic Cu center. The DFT study indicates that the role of Cu center acts as a binding site for alkyne substrate, while activating its terminal C-H bond.

LANDSLIDE RISK MANAGEMENT IN THE COASTAL ZONE OF THE KUIBYSHEV RESERVOIR DUE THE DESIGN OF HIGH-SPEED LINE "MOSCOW-KAZAN"

2017 ◽  
Author(s):  
Nikolai Petrov ◽  
Nikolai Petrov ◽  
Inna Nikonorova ◽  
Inna Nikonorova ◽  
Vladimir Mashin ◽  
...  
Keyword(s):  
High Speed ◽  
Computational Models ◽  
Stable State ◽  
Landslide Risk ◽  
Kuibyshev Reservoir ◽  
Stepped Surface ◽  
The Stability ◽  
Landslide Slope ◽  
The Village

High-speed railway "Moscow-Kazan" by the draft crosses the Volga (Kuibyshev reservoir) in Chuvashia region 500 m below the village of New Kushnikovo. The crossing plot is a right-bank landslide slope with a stepped surface. Its height is 80 m; the slope steepness -15-16o. The authors should assess the risk of landslides and recommend anti-landslide measures to ensure the safety of the future bridge. For this landslide factors have been analyzed, slope stability assessment has been performed and recommendations have been suggested. The role of the following factors have been analyzed: 1) hydrologic - erosion and abrasion reservoir and runoff role; 2) lithologyc (the presence of Urzhum and Northern Dvina horizons of plastically deformable rocks, displacement areas); 3) hydrogeological (the role of perched, ground and interstratal water); 4) geomorphological (presence of the elemental composition of sliding systems and their structure in the relief); 5) exogeodynamic (cycles and stages of landslide systems development, mechanisms and relationship between landslide tiers of different generations and blocks contained in tiers). As a result 6-7 computational models at each of the three engineering-geological sections were made. The stability was evaluated by the method “of the leaning slope”. It is proved that the slope is in a very stable state and requires the following measures: 1) unloading (truncation) of active heads blocks of landslide tiers) and the edge of the plateau, 2) regulation of the surface and groundwater flow, 3) concrete dam, if necessary.

Stability and Folding of the Unusually Stable Hemoglobin from Synechocystis is Subtly Optimized and Dependent on the Key Heme Pocket Residues.

2020 ◽  
Vol 27 ◽  
Author(s):  
Sheetal Uppal ◽  
Mohd. Asim Khan ◽  
Suman Kundu
Keyword(s):  
Molten Globule ◽  
Life Forms ◽  
Model System ◽  
Heme Pocket ◽  
The Past ◽  
Specific Manner ◽  
Delivery Vehicles ◽  
The Stability ◽  
Key Residues ◽  
Synechocystis Sp

Aims: The aim of our study is to understand the biophysical traits that govern the stability and folding of Synechocystis hemoglobin, a unique cyanobacterial globin that displays unusual traits not observed in any of the other globins discovered so far. Background: For the past few decades, classical hemoglobins such as vertebrate hemoglobin and myoglobin have been extensively studied to unravel the stability and folding mechanisms of hemoglobins. However, the expanding wealth of hemoglobins identified in all life forms with novel properties, like heme coordination chemistry and globin fold, have added complexity and challenges to the understanding of hemoglobin stability, which has not been adequately addressed. Here, we explored the unique truncated and hexacoordinate hemoglobin from the freshwater cyanobacterium Synechocystis sp. PCC 6803 known as “Synechocystis hemoglobin (SynHb)”. The “three histidines” linkages to heme are novel to this cyanobacterial hemoglobin. Objective: Mutational studies were employed to decipher the residues within the heme pocket that dictate the stability and folding of SynHb. Methods: Site-directed mutants of SynHb were generated and analyzed using a repertoire of spectroscopic and calorimetric tools. Result: The results revealed that the heme was stably associated to the protein under all denaturing conditions with His117 playing the anchoring role. The studies also highlighted the possibility of existence of a “molten globule” like intermediate at acidic pH in this exceptionally thermostable globin. His117 and other key residues in the heme pocket play an indispensable role in imparting significant polypeptide stability. Conclusion: Synechocystis hemoglobin presents an important model system for investigations of protein folding and stability in general. The heme pocket residues influenced the folding and stability of SynHb in a very subtle and specific manner and may have been optimized to make this Hb the most stable known as of date. Other: The knowledge gained hereby about the influence of heme pocket amino acid side chains on stability and expression is currently being utilized to improve the stability of recombinant human Hbs for efficient use as oxygen delivery vehicles.

Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment

2019 ◽  
Vol 18 (3) ◽  
pp. 232-238 ◽  
Author(s):  
Emanuela Onesti ◽  
Vittorio Frasca ◽  
Marco Ceccanti ◽  
Giorgio Tartaglia ◽  
Maria Cristina Gori ◽  
...  
Keyword(s):  
Pilot Study ◽  
Myasthenia Gravis ◽  
Repetitive Nerve Stimulation ◽  
Beneficial Effects ◽  
Antibody Titers ◽  
The Stability ◽  
Ultramicronized Palmitoylethanolamide ◽  
Open Pilot

Background: The cannabinoid system may be involved in the humoral mechanisms at the neuromuscular junction. Ultramicronized-palmitoylethanolamide (μm-PEA) has recently been shown to reduce the desensitization of Acetylcholine (ACh)-evoked currents in denervated patients modifying the stability of ACh receptor (AChR) function. <p> Objective: To analyze the possible beneficial effects of μm-PEA in patients with myasthenia gravis (MG) on muscular fatigue and neurophysiological changes. <p> Method: The duration of this open pilot study, which included an intra-individual control, was three weeks. Each patient was assigned to a 1-week treatment period with μm-PEA 600 mg twice a day. A neurophysiological examination based on repetitive nerve stimulation (RNS) of the masseteric and the axillary nerves was performed, and the quantitative MG (QMG) score was calculated in 22 MG patients every week in a three-week follow-up period. AChR antibody titer was investigated to analyze a possible immunomodulatory effect of PEA in MG patients. <p> Results: PEA had a significant effect on the QMG score (p=0.03418) and on RNS of the masseteric nerve (p=0.01763), thus indicating that PEA reduces the level of disability and decremental muscle response. Antibody titers did not change significantly after treatment. <p> Conclusion: According to our observations, μm-PEA as an add-on therapy could improve muscular response to fatigue in MG. The possible modulation of AChR currents as a means of eliciting a direct effect from PEA on the conformation of ACh receptors should be investigated. The co-role of cytokines also warrants an analysis. Given the rapidity and reversibility of the response, we suppose that PEA acts directly on AChR, though further studies are needed to confirm this hypothesis.

Sign in / Sign up

Export Citation Format

Share Document