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Non-structural protein 1

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https://www.readbyqxmd.com/read/28746382/gelatin-nanoparticles-enhance-delivery-of-hepatitis-c-virus-recombinant-ns2-gene
#1
Salwa Sabet, Marina A George, Haidan M El-Shorbagy, Heba Bassiony, Khaled Y Farroh, Tareq Youssef, Taher A Salaheldin
BACKGROUND: Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. AIM OF WORK: The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system...
2017: PloS One
https://www.readbyqxmd.com/read/28743743/characterization-of-a-stable-hiv-1-b-c-recombinant-soluble-and-trimeric-envelope-glycoprotein-env-highly-resistant-to-cd4-induced-conformational-changes
#2
Rajesh Kumar, Gabriel Ozorowski, Vivek Kumar, Lauren G Holden, Tripti Shrivastava, Shilpa Patil, Suprit Deshpande, Andrew B Ward, Jayanta Bhattacharya
The HIV-1 envelope (Env) is a glycoprotein which is a trimer of heterodimer containing gp120 and gp41 subunits, mediates virus entry and is a major target of broadly neutralizing antibodies (bnAbs) developed during infection in some individuals. The engagement of the HIV-1 gp120 glycoprotein to the host CD4 protein triggers conformational changes in gp120 that allows its binding to coreceptors, and is necessary for virus entry to establish infection. Native-like HIV-1 Env immunogens representing distinct clades have been proposed to improve immunogenicity of bnAbs...
July 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28742972/stimuli-responsive-directional-vesicular-assembly-with-tunable-surface-functionality-and-impact-on-enzyme-inhibition
#3
Amrita Sikder, Debes Ray, Vinod Kumar Aswal, Suhrit Ghosh
The article describes self-assembly of a series of unsymmetrical bola-shape π-amphiphiles (NDI-1, NDI-1a, NDI-2, NDI-3 and NDI-4) consisting of a hydrophobic naphthalene-diimide (NDI) chromophore attached with a non-ionic hydrophilic wedge and an anionic head group in the two opposite arms of the central NDI. By design only a single hydrazide group is linked either on the ionic or non-ionic arm of the NDI. NDI-1 and NDI-1a are regioisomers differing only in the location of the hydrazide group, placed in the non-ionic or ionic arm, respectively...
July 25, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28742344/insights-into-the-molybdenum-copper-heterometallic-cluster-assembly-in-the-orange-protein-probing-intermolecular-interactions-with-an-artificial-metal-binding-atcun-tag
#4
Biplab K Maiti, Rui M Almeida, Luisa B Maia, Isabel Moura, José J G Moura
Orange protein (ORP) is a small bacterial protein, of unknown function, that contains a unique molybdenum/copper heterometallic cluster, [S2Mo(VI)S2Cu(I)S2Mo(VI)S2](3-) (Mo/Cu), non-covalently bound. The native cluster can be reconstituted in a protein-assisted mode by the addition of Cu(II) plus tetrathiomolybdate to apo-ORP under controlled conditions. In the work described herein, we artificially inserted the ATCUN ("amino terminus Cu and Ni") motif in the Desulfovibrio gigas ORP (Ala1Ser2His3 followed by the native amino acid residues; modified protein abbreviated as ORP*) to increase our understanding of the Mo/Cu cluster assembly in ORP...
July 25, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28739804/role-of-the-disulfide-bond-in-stabilizing-and-folding-of-the-fimbrial-protein-drae-from-uropathogenic-escherichia-coli
#5
Justyna Pilipczuk, Beata Zalewska-Piątek, Piotr Bruździak, Jacek Czub, Milosz Wieczór, Marcin Olszewski, Marta Wanarska, Bogdan Nowicki, Danuta Augustin-Nowacka, Rafal Piątek
Dr fimbriae are homopolymeric adhesive organelles of uropathogenic Escherichia coli composed of DraE subunits, responsible for the attachment to host cells. These structures are characterized by enormously high stability resulting from the structural properties of an Ig-like fold of DraE. One feature of DraE and other fimbrial subunits that makes them peculiar among Ig-like domain-containing proteins is a conserved disulfide bond that joins their A and B strands. Here, we investigated how this disulfide bond affects the stability and folding/unfolding pathway of DraE...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28737890/a-difluoroboron-%C3%AE-diketonate-probe-shows-turn-on-near-infrared-fluorescence-specific-for-tau-fibrils
#6
Kwang-Su Park, Mi Kyoung Kim, Yujin Seo, Taewoong Ha, Kyeongha Yoo, Seung Jae Hyeon, Yu Jin Hwang, Junghee Lee, Hoon Ryu, Hyunah Choo, Youhoon Chong
Tau aggregation in neuronal cells has recently received significant attention as a robust predictor of the progression of Alzheimer's disease (AD) because of its proven correlation with the degree of cognitive impairment in AD patients. Accordingly, noninvasive imaging of tau aggregates has been highlighted as a promising diagnostic tool for AD. We have previously identified a tau-specific "turn-on" near-infrared fluorescent (NIRF) probe (1), and, in this study, structural modification was performed to optimize its physicochemical as well as fluorescence properties...
July 26, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28736993/molecular-characterization-of-streptococcus-pneumoniae-particularly-serotype19a-st320-that-emerged-in-krasnoyarsk-russia
#7
Irina N Protasova, Tsai-Wen Wan, Natalya V Bakhareva, Wei-Chun Hung, Wataru Higuchi, Yasuhisa Iwao, Tatyana A Yelistratova, Natalya A Ilyenkova, Yelena S Sokolovskaya, Galina P Martynova, Ivan V Reva, Galina V Reva, Sergey V Sidorenko, Lee-Jene Teng, Olga V Peryanova, Alla B Salmina, Tatsuo Yamamoto
Streptococcus pneumoniae, a common human pathogen, colonizes the nasopharynx and causes diseases including acute otitis media (AOM). We herein report pneumococcal serotype distributions in children before and after PCV7 vaccination and in patients with pneumococcal disease in Siberian Russia (Krasnoyarsk). Analyses included antimicrobial susceptibility testing, ST typing, a pulsed-field gel electrophoresis analysis, virulence-related surface protein gene (VSG) typing with novel primers, and a structural analysis by scanning electron microscopy...
July 23, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28736176/crystal-structure-of-the-c-terminal-domain-of-human-eif2d-and-its-implications-on-eukaryotic-translation-initiation
#8
Anand T Vaidya, Ivan B Lomakin, Newlyn N Joseph, Sergey E Dmitriev, Thomas A Steitz
Protein synthesis is a key process in all living organisms. In eukaryotes, Initiation Factor 2 (eIF2) plays an important role in translation initiation as it selects and delivers the initiator tRNA to the small ribosomal subunit. Under stress conditions, phosphorylation of the α-subunit of eIF2 downregulates cellular protein synthesis. However, translation of certain mRNAs continues via the eIF2D dependent non-canonical initiation pathway. The molecular mechanism of this process remains elusive. In addition, eIF2D plays a role in translation re-initiation and ribosome recycling...
July 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28735452/characterization-of-polymeric-substance-classes-in-cereal-based-beverages-using-asymmetrical-flow-field-flow-fractionation-with-a-multi-detection-system
#9
Georg Krebs, Thomas Becker, Martina Gastl
Cereal-based beverages contain a complex mixture of various polymeric macromolecules including polysaccharides, peptides, and polyphenols. The molar mass of polymers and their degradation products affect different technological and especially sensory parameters of beverages. Asymmetrical flow field-flow fractionation (AF4) coupled with multi-angle light scattering (MALS) and refractive index detection (dRI) or UV detection (UV) is a technique for structure and molar mass distribution analysis of macromolecules commonly used for pure compound solutions...
July 22, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28733599/nanoscale-investigation-of-generation-1-pamam-dendrimers-interaction-with-a-protein-nanopore
#10
Alina Asandei, Andrei Ciuca, Aurelia Apetrei, Irina Schiopu, Loredana Mereuta, Chang Ho Seo, Yoonkyung Park, Tudor Luchian
Herein, we describe at uni-molecular level the interactions between poly(amidoamine) (PAMAM) dendrimers of generation 1 and the α-hemolysin protein nanopore, at acidic and neutral pH, and ionic strengths of 0.5 M and 1 M KCl, via single-molecule electrical recordings. The results indicate that kinetics of dendrimer-α-hemolysin reversible interactions is faster at neutral as compared to acidic pH, and we propose as a putative explanation the fine interplay among conformational and rigidity changes on the dendrimer structure, and the ionization state of the dendrimer and the α-hemolysin...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732214/crispr-cas9-technology-based-xenograft-tumors-as-candidate-reference-materials-for-multiple-eml4-alk-rearrangements-testing
#11
Rongxue Peng, Rui Zhang, Guigao Lin, Xin Yang, Ziyang Li, Kuo Zhang, Jiawei Zhang, Jinming Li
The echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (EML4-ALK) rearrangement is an important biomarker that plays a pivotal role in therapeutic decision making for non-small-cell lung cancer (NSCLC) patients. Ensuring accuracy and reproducibility of EML4-ALK testing by fluorescence in situ hybridization, immunohistochemistry, RT-PCR, and next-generation sequencing requires reliable reference materials for monitoring assay sensitivity and specificity...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28729757/protein-protein-interfaces-are-vdw-dominant-with-selective-h-bonds-and-or-electrostatics-towards-broad-functional-specificity
#12
Christina Nilofer, Anshul Sukhwal, Arumugam Mohanapriya, Pandjassarame Kangueane
Several catalysis, cellular regulation, immune function, cell wall assembly, transport, signaling and inhibition occur through Protein- Protein Interactions (PPI). This is possible with the formation of specific yet stable protein-protein interfaces. Therefore, it is of interest to understand its molecular principles using structural data in relation to known function. Several interface features have been documented using known X-ray structures of protein complexes since 1975. This has improved our understanding of the interface using structural features such as interface area, binding energy, hydrophobicity, relative hydrophobicity, salt bridges and hydrogen bonds...
2017: Bioinformation
https://www.readbyqxmd.com/read/28729422/o-glycosylation-modulates-the-stability-of-epidermal-growth-factor-like-repeats-and-thereby-regulates-notch-trafficking
#13
Hideyuki Takeuchi, Hongjun Yu, Huilin Hao, Megumi Takeuchi, Atsuko Ito, Huilin Li, Robert S Haltiwanger
Glycosylation in the endoplasmic reticulum (ER) is closely associated with protein folding and quality control. We recently described a non-canonical ER quality control mechanism for folding of thrombospondin type 1 repeats by Protein O-fucosyltransferase 2 (POFUT2). Epidermal Growth Factor-like (EGF) repeats are also small, cysteine rich protein motifs that can be O-glycosylated by several ER-localized enzymes including Protein O-glucosyltransferase 1 (POGLUT1) and POFUT1. Both POGLUT1 and POFUT1 modify the Notch receptor on multiple EGF repeats and are essential for full Notch function...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724936/an-engineered-protein-antagonist-of-k-ras-b-raf-interaction
#14
Monique J Kauke, Michael W Traxlmayr, Jillian A Parker, Jonathan D Kiefer, Ryan Knihtila, John McGee, Greg Verdine, Carla Mattos, K Dane Wittrup
Ras is at the hub of signal transduction pathways controlling cell proliferation and survival. Its mutants, present in about 30% of human cancers, are major drivers of oncogenesis and render tumors unresponsive to standard therapies. Here we report the engineering of a protein scaffold for preferential binding to K-Ras G12D. This is the first reported inhibitor to achieve nanomolar affinity while exhibiting specificity for mutant over wild type (WT) K-Ras. Crystal structures of the protein R11.1.6 in complex with K-Ras WT and K-Ras G12D offer insight into the structural basis for specificity, highlighting differences in the switch I conformation as the major defining element in the higher affinity interaction...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724759/cholesterol-25-hydroxylase-inhibits-porcine-reproductive-and-respiratory-syndrome-virus-replication-through-enzyme-activity-dependent-and-independent-mechanisms
#15
Wenting Ke, Liurong Fang, Huiyuan Jing, Ran Tao, Ting Wang, Yang Li, Siwen Long, Dang Wang, Shaobo Xiao
Cholesterol 25-hydroxylase (CH25H) has recently been identified as a host restriction factor that exerts antiviral effects by catalyzing the production of 25-hydroxycholesterol (25HC). CH25H can be rapidly induced upon infection with some viruses. Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, has ranked among the most important swine pathogens since it was discovered in the late 1980s. In this study, we found that PRRSV infection significantly downregulated the expression of CH25H in cells by a so far unknown mechanism, suggesting that CH25H might exert antiviral activity against PRRSV...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28722205/temperature-stability-of-proteins-analysis-of-irreversible-denaturation-using-isothermal-calorimetry
#16
Arne Schön, Benjamin R Clarkson, Maria Jaime, Ernesto Freire
The structural stability of proteins has been traditionally studied under conditions in which the folding/unfolding reaction is reversible, since thermodynamic parameters can only be determined under these conditions. Achieving reversibility conditions in temperature stability experiments has often required performing the experiments at acidic pH or other non-physiological solvent conditions. With the rapid development of protein drugs, the fastest growing segment in the pharmaceutical industry, the need to evaluate protein stability under formulation conditions has acquired renewed urgency...
July 19, 2017: Proteins
https://www.readbyqxmd.com/read/28720784/snap-tagged-chikungunya-virus-replicons-improve-visualisation-of-non-structural-protein-3-by-fluorescence-microscopy
#17
Roland Remenyi, Grace C Roberts, Carsten Zothner, Andres Merits, Mark Harris
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes febrile disease, muscle and joint pain, which can become chronic in some individuals. The non-structural protein 3 (nsP3) plays essential roles during infection, but a complete understanding of its function is lacking. Here we used a microscopy-based approach to image CHIKV nsP3 inside human cells. The SNAP system consists of a self-labelling enzyme tag, which catalyses the covalent linking of exogenously supplemented synthetic ligands. Genetic insertion of this tag resulted in viable replicons and specific labelling while preserving the effect of nsP3 on stress granule responses and co-localisation with GTPase Activating Protein (SH3 domain) Binding Proteins (G3BPs)...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720427/the-challenges-and-promise-of-targeting-the-liver-x-receptors-for-treatment-of-inflammatory-disease
#18
REVIEW
Michael B Fessler
The Liver X Receptors (LXRs) are oxysterol-activated transcription factors that upregulate a suite of genes that together promote coordinated mobilization of excess cholesterol from cells and from the body. The LXRs, like other nuclear receptors, are anti-inflammatory, inhibiting signal-dependent induction of pro-inflammatory genes by nuclear factor-κB, activating protein-1, and other transcription factors. Synthetic LXR agonists have been shown to ameliorate atherosclerosis and a wide range of inflammatory disorders in preclinical animal models...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28718943/hepatitis-e-virus-orf-1-induces-proliferative-and-functional-t-cell-responses-in-patients-with-ongoing-and-resolved-hepatitis-e
#19
Jana Al-Ayoubi, Patrick Behrendt, Birgit Bremer, Pothakamuri Venkata Suneetha, Anett Gisa, Franziska Rinker, Michael P Manns, Markus Cornberg, Heiner Wedemeyer, Anke R M Kraft
BACKGROUND AND AIMS: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis with > 3 million symptomatic cases per year accounting for 70,000 HEV-related deaths. HEV-specific T-cell responses have been investigated against structural proteins expressed by open reading frames (ORF) 2 and 3. T-cell responses against non-structural HEV proteins encoded by ORF1 are hardly studied. The aim of this study was to determine HEV ORF1-specific T-cell responses in comparison to ORF2/3 in patients exposed to HEV...
July 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28718627/structural-basis-for-interaction-of-the-tandem-zinc-finger-domains-of-human-muscleblind-with-cognate-rna-from-human-cardiac-troponin-t
#20
Sangho Park, Priti Deka Phukan, Markus Zeeb, Maria A Martinez-Yamout, Helen Jane Dyson, Peter E Wright
The human muscleblind-like proteins (MBNL) regulate tissue-specific splicing by targeting cardiac troponin T and other pre-mRNAs; aberrant targeting of CUG and CCUG repeat expansions frequently accompanies the neuromuscular disease myotonic dystrophy. We show, using biolayer interferometry (Octet), and NMR spectroscopy, that the zinc finger domains of MBNL isoform 1 (MBNL1) are necessary and sufficient for binding CGCU sequences within the pre-mRNA of human cardiac troponin T (hcTnT). Protein constructs containing zinc fingers 1 and 2 (zf12) and zinc fingers 3 and 4 (zf34) of MBNL1 each fold into a compact globular tandem zinc finger structure that participates in RNA binding...
July 18, 2017: Biochemistry
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