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https://www.readbyqxmd.com/read/28231312/analysis-of-the-t-cell-response-to-zika-virus-and-identification-of-a-novel-cd8-t-cell-epitope-in-immunocompetent-mice
#1
Ryan D Pardy, Maaran M Rajah, Stephanie A Condotta, Nathan G Taylor, Selena M Sagan, Martin J Richer
Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family. Although ZIKV infection is typically mild and self-limiting in healthy adults, infection has been associated with neurological symptoms such as Guillain-Barré syndrome, and a causal link has been established between fetal microcephaly and ZIKV infection during pregnancy. These risks, and the magnitude of the ongoing ZIKV pandemic, have created an urgent need for the development of animal models to study the immune response to ZIKV infection...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28225274/a-rational-design-of-a-selective-inhibitor-for-kv1-1-channels-prevalent-in-demyelinated-nerves-that-improves-their-impaired-axonal-conduction
#2
Ahmed Al-Sabi, Declan Daly, Patrick Hoefer, Gemma K Kinsella, Charles P E Metais, Mark Pickering, Caroline Herron, Seshu Kumar Kaza, Kieran J Nolan, J Oliver Dolly
K(+) channels containing Kv1.1 α subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarising K(+) currents. Modelling of interactions with the extracellular pore in a Kv1.1 deduced-structure identified a diaryldi-(2-pyrrolyl)methane (DPM) as a suitable scaffold, with optimised alkyl ammonium side chains. The resultant synthesised candidate [2,2'-((5,5'(di-p-topyldiaryldi-(2-pyrrolyl)methane)bis(2,2'carbonyl)bis (azanediyl)) diethaneamine...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28224210/tumor-specific-regulatory-t-cells-in-the-bone-marrow-of-breast-cancer-patients-selectively-upregulate-the-emigration-receptor-s1p1
#3
Anchana Rathinasamy, Christoph Domschke, Yingzi Ge, Hans-Henning Böhm, Steffen Dettling, David Jansen, Felix Lasitschka, Ludmila Umansky, Markus H Gräler, Jennifer Hartmann, Christel Herold-Mende, Florian Schuetz, Philipp Beckhove
Regulatory T cells (Treg) hamper anti-tumor T-cell responses resulting in reduced survival and failure of cancer immunotherapy. Among lymphoid organs, the bone marrow (BM) is a major site of Treg residence and recirculation. However, the process governing the emigration of Treg from BM into the circulation remains elusive. We here show that breast cancer patients harbour reduced Treg frequencies in the BM as compared to healthy individuals or the blood. This was particularly the case for tumor antigen-specific Treg which were quantified by MHCII tumor peptide loaded tetramers...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28221768/formation-of-nitrogenase-nifdk-tetramers-in-the-mitochondria-of-saccharomyces-cerevisiae
#4
Stefan Burén, Eric M Young, Elizabeth A Sweeny, Gema López-Torrejón, Marcel Veldhuizen, Christopher A Voigt, Luis M Rubio
Transferring the prokaryotic enzyme nitrogenase into a eukaryotic host with the final aim of developing N2 fixing cereal crops would revolutionize agricultural systems worldwide. Targeting it to mitochondria has potential advantages because of the organelle's high O2 consumption and the presence of bacterial-type iron-sulfur cluster biosynthetic machinery. In this study, we constructed 96 strains of Saccharomyces cerevisiae where transcriptional units comprising nine Azotobacter vinelandii nif genes (nifHDKUSMBEN) were integrated into the genome...
February 21, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28213736/6-phosphofructokinase-and-ribulose-5-phosphate-3-epimerase-in-methylotrophic-bacillus-methanolicus-ribulose-monophosphate-cycle
#5
Simone Balzer Le, Tonje Marita Bjerkan Heggeset, Tone Haugen, Ingemar Nærdal, Trygve Brautaset
D-Ribulose-5-phosphate-3-epimerase (RPE) and 6-phosphofructokinase (PFK) catalyse two reactions in the ribulose monophosphate (RuMP) cycle in Bacillus methanolicus. The B. methanolicus wild-type strain MGA3 possesses two putative rpe and pfk genes encoded on plasmid pBM19 (rpe1-MGA3 and pfk1-MGA3) and on the chromosome (rpe2-MGA3 and pfk2-MGA3). The wild-type strain PB1 also encodes putative rpe and pfk genes on plasmid pBM20 (rpe1-PB1 and pfk1-PB1*); however, it only harbours a chromosomal pfk gene (pfk2-PB1)...
February 17, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28212295/short-chain-chitin-oligomers-promoters-of-plant-growth
#6
Alexander J Winkler, Jose Alfonso Dominguez-Nuñez, Inmaculada Aranaz, César Poza-Carrión, Katrina Ramonell, Shauna Somerville, Marta Berrocal-Lobo
Chitin is the second most abundant biopolymer in nature after cellulose, and it forms an integral part of insect exoskeletons, crustacean shells, krill and the cell walls of fungal spores, where it is present as a high-molecular-weight molecule. In this study, we showed that a chitin oligosaccharide of lower molecular weight (tetramer) induced genes in Arabidopsis that are principally related to vegetative growth, development and carbon and nitrogen metabolism. Based on plant responses to this chitin tetramer, a low-molecular-weight chitin mix (CHL) enriched to 92% with dimers (2mer), trimers (3mer) and tetramers (4mer) was produced for potential use in biotechnological processes...
February 15, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28211917/concentration-dependent-oligomerization-of-an-alpha-helical-antifreeze-polypeptide-makes-it-hyperactive
#7
Sheikh Mahatabuddin, Yuichi Hanada, Yoshiyuki Nishimiya, Ai Miura, Hidemasa Kondo, Peter L Davies, Sakae Tsuda
A supersoluble 40-residue type I antifreeze protein (AFP) was discovered in a righteye flounder, the barfin plaice (bp). Unlike all other AFPs characterized to date, bpAFP transitions from moderately-active to hyperactive with increasing concentration. At sub-mM concentrations, bpAFP bound to pyramidal planes of ice to shape it into a bi-pyramidal hexagonal trapezohedron, similarly to the other moderately-active AFPs. At mM concentrations, bpAFP uniquely underwent further binding to the whole ice crystal surface including the basal planes...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211453/mechanism-of-partial-agonism-in-ampa-type-glutamate-receptors
#8
Hector Salazar, Clarissa Eibl, Miriam Chebli, Andrew Plested
Neurotransmitters trigger synaptic currents by activating ligand-gated ion channel receptors. Whereas most neurotransmitters are efficacious agonists, molecules that activate receptors more weakly-partial agonists-also exist. Whether these partial agonists have weak activity because they stabilize less active forms, sustain active states for a lesser fraction of the time or both, remains an open question. Here we describe the crystal structure of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) ligand binding domain (LBD) tetramer in complex with the partial agonist 5-fluorowillardiine (FW)...
February 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28205250/crystal-structure-of-dibenzothiophene-sulfone-monooxygenase-bdsa-from-bacillus-subtilis-wu-s2b
#9
Masahiko Okai, Woo Cheol Lee, Li-Jun Guan, Takashi Ohshiro, Yoshikazu Izumi, Masaru Tanokura
The dibenzothiophene (DBT) sulfone monooxygenase BdsA from Bacillus subtilis WU-S2B catalyzes the conversion of DBT sulfone to 2'-hydroxybiphenyl 2-sulfinate (HBPS). We report the crystal structures of BdsA at a resolution of 2.80 Å. BdsA exists as a homotetramer with a dimer-of-dimers configuration in the crystal, and the interaction between E288 and R296 in BdsA is important for tetramer formation. A structural comparison with homologous proteins shows that the orientation and location of the α9-α12 helices in BdsA are closer to those of the closed form than those of the open form in the EDTA monooxygenase EmoA...
February 16, 2017: Proteins
https://www.readbyqxmd.com/read/28205095/tetramerization-of-satb1-is-essential-for-regulating-of-gene-expression
#10
Minying Zheng, Wancai Xing, Yabing Liu, Meng Li, Hao Zhou
Special AT-rich sequence-binding protein 1 (SATB1) functions as a 'genome organizer' in tumorigenesis. Our previous report showed that SATB1 forms a tetramer through its N-terminal ubiquitin like domain rather than the proposed PDZ domain. In the present study, we aim to illustrate whether this oligomerization is critical to its function as a global repressor of gene expression in vivo. Luciferase and GST pull-down assays demonstrated that disrupting SATB1's tetramerization not only affects the activities of promoters but also influences the recruitment of interaction partners...
February 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28202889/treatment-of-transthyretin-familial-amyloid-polyneuropathy-with-tafamidis-a-case-report
#11
Yoshimichi Miyazaki
INTRODUCTION: Familial amyloid polyneuropathy (FAP) is a rare hereditary disorder caused by mutations in the transthyretin (TTR) gene. Tafamidis is a TTR stabilizer able to prevent TTR tetramer dissociation, and several studies have demonstrated its safety and efficacy at slowing the progression of neuropathy in FAP caused by the TTR Val30Met mutation. However, nerve conduction study (NCS) and electromyography (EMG) results have yet to be reported in relation to FAP progression during tafamidis therapy...
2017: Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics
https://www.readbyqxmd.com/read/28202467/a-key-centriole-assembly-interaction-interface-between-human-plk4-and-stil-appears-to-not-be-conserved-in-flies
#12
Matthew A Cottee, Steven Johnson, Jordan W Raff, Susan M Lea
A small number of proteins form a conserved pathway of centriole duplication. In humans and flies, the binding of Plk4/Sak to STIL/Ana2 initiates daughter centriole assembly. In humans, this interaction is mediated by an interaction between the Polo-Box-3 (PB3) domain of Plk4 and the coiled-coil domain of STIL (HsCCD). We showed previously that the Drosophila Ana2 coiled-coil domain (DmCCD) is essential for centriole assembly, but it forms a tight parallel tetramer in vitro that likely precludes an interaction with PB3...
February 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28196863/conformational-changes-in-the-activation-loop-of-mitochondrial-glutaminase-c-a-direct-fluorescence-read-out-that-distinguishes-the-binding-of-allosteric-inhibitors-from-activators
#13
Clint A Stalnecker, Jon W Erickson, Richard A Cerione
The first step in glutamine catabolism is catalyzed by the mitochondrial enzyme glutaminase, with a specific isoform, glutaminase C (GAC), being highly expressed in cancer cells. GAC activation requires the formation of homo-tetramers, promoted by anionic allosteric activators such as inorganic phosphate. This leads to the proper orientation of a flexible loop proximal to the dimer-dimer interface that is essential for catalysis (i.e. the activation loop). A major class of allosteric inhibitors of GAC, with the prototype being BPTES (bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide), and the related molecule CB-839, binds to the activation loop and induces the formation of an inactive tetramer (2 inhibitors bound per active tetramer)...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28193903/structural-analysis-of-mycobacterium-tuberculosis-homologues-of-the-eukaryotic-proteasome-assembly-chaperone-2-pac2
#14
Lin Bai, Jordan B Jastrab, Marta Isasa, Kuan Hu, Hongjun Yu, Steven P Gygi, K Heran Darwin, Huilin Li
A previous bioinformatics analysis identified the Mycobacterium tuberculosis (M. tuberculosis) proteins Rv2125 and Rv2714 as orthologs of the eukaryotic proteasome assembly chaperone 2 (PAC2). We set out to investigate whether Rv2125 or Rv2714 could function in proteasome assembly. We solved the crystal structure of Rv2125 at 3.0 Å resolution, which showed an overall fold similar to that of the PAC2 family proteins that include the archaeal PbaB and the yeast Pba1. However, Rv2125 and Rv2714 formed trimers, whereas PbaB forms tetramers and Pba1 dimerizes with Pba2...
February 13, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28184005/a-c-terminal-tail-region-in-the-rous-sarcoma-virus-integrase-provides-high-plasticity-of-functional-integrase-oligomerization-during-intasome-assembly
#15
Krishan K Pandey, Sibes Bera, Ke Shi, Hideki Aihara, Duane P Grandgenett
The retrovirus integrase (IN) inserts the viral cDNA into the host DNA genome. Atomic structures of five different retrovirus INs complexed with their respective viral DNA or branched viral/target DNA substrates have indicated these intasomes are composed of IN subunits ranging from tetramers, to octamers or to hexadecamers. IN precursors are monomers, dimers or tetramers in solution. But, how intasome assembly is controlled remains unclear. Therefore, we sought to unravel the functional mechanisms in different intasomes...
February 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28181678/safety-and-immunological-efficacy-of-a-dna-vaccine-encoding-the-androgen-receptor-ligand-binding-domain-ar-lbd
#16
Brian M Olson, Eric S Bradley, Thomas Sawicki, Weixiong Zhong, Erik A Ranheim, Jordan E Bloom, Viswa T Colluru, Laura E Johnson, Brian T Rekoske, Jens C Eickhoff, Douglas G McNeel
BACKGROUND: The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR...
February 9, 2017: Prostate
https://www.readbyqxmd.com/read/28174302/free-energy-landscape-remodeling-of-the-cardiac-pacemaker-channel-explains-the-molecular-basis-of-familial-sinus-bradycardia
#17
Stephen Boulton, Madoka Akimoto, Sam Akbarizadeh, Giuseppe Melacini
The hyperpolarization-activated and cyclic-nucleotide modulated ion channel (HCN) drives the pacemaker activity in the heart, and its malfunction can result in heart disorders. One such disorder, familial sinus bradycardia, is caused by the S672R mutation in HCN, whose electrophysiological phenotypes include a negative shift in the channel activation voltage and an accelerated HCN deactivation. The outcomes of these changes are abnormally low resting heart rates. However, the molecular mechanism underlying these electrophysiological changes is currently not fully understood...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28174261/identification-of-unique-antigenic-determinants-in-the-amino-terminus-of-ia-2-ica512-in-childhood-and-adult-autoimmune-diabetes-new-biomarker-development
#18
Maria Acevedo-Calado, Eddie A James, Michael P Morran, Susan L Pietropaolo, Qin Ouyang, David Arribas-Layton, Marco Songini, Marco Liguori, Anna Casu, Richard J Auchus, Shuai Huang, Liping Yu, Aaron Michels, Roberto Gianani, Massimo Pietropaolo
OBJECTIVE: The characterization of diverse subtypes of diabetes is a dynamic field of clinical research and an active area of discussion. The objective of this study was to identify new antigenic determinants in the neuroendocrine autoantigen IA-2 (ICA512) and assess whether circulating autoantibodies directed to new IA-2 epitopes identify autoimmune diabetes in young and adult populations with diabetes. RESEARCH DESIGN AND METHODS: Clinically diagnosed patients with type 2 diabetes (n = 258; diabetes duration: 0...
February 7, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28151660/surprisingly-high-selectivity-and-high-affinity-in-mercury-recognition-by-h-bonded-cavity-containing-aromatic-foldarands
#19
Jie Shen, Changliang Ren, Huaqiang Zeng
In the absence of macrocyclic ring constraints, few synthetic systems, possessing a mostly solvent-independent well-folded conformation that is predisposed for highly selective and high affinity recognition of metal ions, have been demonstrated. We report here such a unique class of conformationally robust modularly tunable folding molecules termed foldarands that can recognize Hg2+ ions surprisingly well over 22 other metal ions. Despite of lack of sulfur atoms and having only oxygen-donor atoms in its structure, the best foldarand molecule, i...
February 2, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28145069/crystal-structures-of-diaryliodonium-fluorides-and-their-implications-for-fluorination-mechanisms
#20
Yong Sok Lee, Joong-Hyun Chun, Milan Hodošček, Victor Pike
The radiofluorination of diaryliodonium salts is of value for producing radiotracers for positron emission tomography. We report crystal structures for two diaryliodonium fluorides. Whereas diphenyliodon um fluoride (1a) exists as a tetramer bridged by four fluoride ions, 2-methylphenyl(phenyl)iodonium fluoride (2a) forms a fluoride-bridged dimer that is further halogen-bonded to two other monomers. We discuss the topological relationships between the two and their implications for fluorination in solution...
January 31, 2017: Chemistry: a European Journal
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