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https://www.readbyqxmd.com/read/28636952/human-leukocyte-antigen-f-presents-peptides-and-regulates-immunity-through-interactions-with-nk-cell-receptors
#1
Charles L Dulberger, Curtis P McMurtrey, Angelique Hölzemer, Karlynn E Neu, Victor Liu, Adriana M Steinbach, Wilfredo F Garcia-Beltran, Michael Sulak, Bana Jabri, Vincent J Lynch, Marcus Altfeld, William H Hildebrand, Erin J Adams
Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#2
Jacob Glanville, Huang Huang, Allison Nau, Olivia Hatton, Lisa E Wagar, Florian Rubelt, Xuhuai Ji, Arnold Han, Sheri M Krams, Christina Pettus, Nikhil Haas, Cecilia S Lindestam Arlehamn, Alessandro Sette, Scott D Boyd, Thomas J Scriba, Olivia M Martinez, Mark M Davis
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636205/progressive-scar14-with-unclear-speech-developmental-delay-tremor-and-behavioral-problems-caused-by-a-homozygous-deletion-of-the-sptbn2-pleckstrin-homology-domain
#3
Esra Yıldız Bölükbaşı, Muhammad Afzal, Sara Mumtaz, Nafees Ahmad, Sajid Malik, Aslıhan Tolun
We report on nine members of a consanguineous Pakistani family with primary presentation of intellectual disability, developmental delay, limb and gait ataxia, behavioral and speech problems, and tremor. By linkage mapping and exome sequencing we identified novel homozygous splicing variant c.6375-1G>C in SPTBN2. To date, only two other SPTBN2 mutations with recessive pattern of inheritance causing SCAR14 (spinocerebellar ataxia, autosomal recessive 14) that manifest with developmental ataxia and cognitive impairment, or cerebellar ataxia, mental retardation, and pyramidal signs have been reported...
June 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28631469/the-chemical-composition-of-blackberry-press-cake-polyphenolic-extract-and-defatted-seeds-and-their-effects-on-cecal-fermentation-bacterial-metabolites-and-blood-lipid-profile-in-rats
#4
Monika Kosmala, Adam Jurgonski, Jerzy Juskiewicz, Elżbieta Karlińska, Jakub Macierzyński, Edward Roj, Zenon Zduńczyk
Blackberry fiber (BF), extracted blackberry fiber (EBF), defatted blackberry seeds (DBS) and blackberry polyphenols (BP) were added to diets of rats. A control diet, fiber diets (BF, EBF, DBS) with 6% addition instead of cellulose, a polyphenol diet (BP) with 1% addition were administered for 4 weeks. BF and DBS contained polyphenols (3.6%), EBF did not. DBS was free of fat. Ellagitannins were the main phenolics; mostly dimers (sanguiin H-6 with isomers) and monomers (pedunculagin, casuarictin isomer, and sanguiin H-2 isomer)...
June 20, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28630893/a-d53-repression-motif-induces-oligomerization-of-topless-corepressors-and-promotes-assembly-of-a-corepressor-nucleosome-complex
#5
Honglei Ma, Jingbo Duan, Jiyuan Ke, Yuanzheng He, Xin Gu, Ting-Hai Xu, Hong Yu, Yonghong Wang, Joseph S Brunzelle, Yi Jiang, Scott B Rothbart, H Eric Xu, Jiayang Li, Karsten Melcher
TOPLESS are tetrameric plant corepressors of the conserved Tup1/Groucho/TLE (transducin-like enhancer of split) family. We show that they interact through their TOPLESS domains (TPDs) with two functionally important ethylene response factor-associated amphiphilic repression (EAR) motifs of the rice strigolactone signaling repressor D53: the universally conserved EAR-3 and the monocot-specific EAR-2. We present the crystal structure of the monocot-specific EAR-2 peptide in complex with the TOPLESS-related protein 2 (TPR2) TPD, in which the EAR-2 motif binds the same TPD groove as jasmonate and auxin signaling repressors but makes additional contacts with a second TPD site to mediate TPD tetramer-tetramer interaction...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28630092/characterization-of-high-avidity-cytomegalovirus-specific-t-cells-with-differential-tetramer-binding-coappearing-after-allogeneic-stem-cell-transplantation
#6
Justyna Ogonek, Kriti Verma, Christian Schultze-Florey, Pavankumar Varanasi, Susanne Luther, Patrick Schweier, Wolfgang Kühnau, Gudrun Göhring, Elke Dammann, Michael Stadler, Arnold Ganser, Ulrike Koehl, Christian Koenecke, Eva M Weissinger, Lothar Hambach
CMV reactivation is a major complication after allogeneic stem cell transplantation (SCT). Immune reconstitution of CMV-specific CTLs (CMV-CTLs) is essential for virus control. During CMV-CTL monitoring using mutated HLA/CMV tetramers selectively detecting high-avidity T cells, we observed coappearance of CMV-CTLs with low (CMV tet(low) CTLs) and high tetramer binding (CMV tet(high) CTLs) in 53/115 CMV IgG(+) patients stem cell transplanted from CMV IgG(+) donors. However, the relevance of these coappearing differentially tetramer binding ("dual") CMV-CTLs was unclear...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28625911/white-shrimp-litopenaeus-vannamei-recombinant-lactate-dehydrogenase-biochemical-and-kinetic-characterization
#7
Ambar A Fregoso-Peñuñuri, Elisa M Valenzuela-Soto, Ciria G Figueroa-Soto, Alma B Peregrino-Uriarte, Manuel Ochoa-Valdez, Lilia Leyva-Carrillo, Gloria Yepiz-Plascencia
Shrimp lactate dehydrogenase (LDH) is induced in response to environmental hypoxia. Two protein subunits deduced from different transcripts of the LDH gene from the shrimp Litopenaeus vannamei (LDHvan-1 and LDHvan-2) were identified. These subunits are expressed by alternative splicing. Since both subunits are expressed in most tissues, the purification of the enzyme from the shrimp will likely produce hetero LDH containing both subunits. Therefore, the aim of this study was to overexpress, purify and characterize only one subunit as a recombinant protein, the LDHvan-2...
June 15, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28625364/semi-quantitative-models-for-identifying-potent-and-selective-transthyretin-amyloidogenesis-inhibitors
#8
Stephen Connelly, David E Mortenson, Sungwook Choi, Ian A Wilson, Evan T Powers, Jeffery W Kelly, Steven M Johnson
Rate-limiting dissociation of the tetrameric protein transthyretin (TTR), followed by monomer misfolding and misassembly, appears to cause degenerative diseases in humans known as the transthyretin amyloidoses, based on human genetic, biochemical and pharmacologic evidence. Small molecules that bind to the generally unoccupied thyroxine binding pockets in the native TTR tetramer kinetically stabilize the tetramer, slowing subunit dissociation proportional to the extent that the molecules stabilize the native state over the dissociative transition state-thereby inhibiting amyloidogenesis...
May 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28623196/origin-single-stranded-dna-releases-sld3-protein-from-the-mcm2-7-complex-allowing-the-gins-tetramer-to-bind-the-mcm2-7-complex
#9
Irina Bruck, Daniel L Kaplan
No abstract text is available yet for this article.
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28623126/crystal-structure-of-trna-his-guanylyltransferase-from-saccharomyces-cerevisiae
#10
Kitaik Lee, Eun Hye Lee, Jonghyeon Son, Kwang Yeon Hwang
tRNA maturation involves several steps, including processing, splicing, CCA addition, and posttranscriptional modifications. tRNA(His) guanylyltransferase (Thg1) is the only enzyme known to catalyze templated nucleotide addition in the 3'-5' direction, unlike other DNA and RNA polymerases. For a better understanding of its unique catalytic mechanism at the molecular level, we determined the crystal structure of GTP-bound Thg1 from Saccharomyces cerevisiae at the maximum resolution of 3.0 Å. The structure revealed the enzyme to have a tetrameric conformation that is well conserved among different species, and the GTP molecule was clearly bound at the active site, coordinating with two magnesium ions...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28622347/rna-guided-transcriptional-activation-via-crispr-dcas9-mimics-overexpression-phenotypes-in-arabidopsis
#11
Jong-Jin Park, Emma Dempewolf, Wenzheng Zhang, Zeng-Yu Wang
Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR associated protein 9 (Cas9) system allows effective gene modification through RNA-guided DNA targeting. The Cas9 has undergone a series of functional alterations from the original active endonuclease to partially or completely deactivated Cas9. The catalytically deactivated Cas9 (dCas9) offers a platform to regulate transcriptional expression with the addition of activator or repressor domains. We redesigned a CRISPR/Cas9 activation system by adding the p65 transactivating subunit of NF-kappa B and a heat-shock factor 1 (HSF) activation domain to dCas9 bound with the VP64 (tetramer of VP16) activation domain for application in plants...
2017: PloS One
https://www.readbyqxmd.com/read/28621364/single-molecule-probing-of-amyloid-nano-ensembles-using-the-polymer-nanoarray-approach
#12
Sibaprasad Maity, Ekaterina Viazovkina, Alexander Gall, Yuri L Lyubchenko
Soluble amyloid-beta (Aβ) oligomers are the prime causative agents of cognitive deficits during early stages of Alzheimer's disease (AD). The transient nature of the oligomers makes them difficult to characterize by traditional techniques, suggesting that advanced approaches are necessary. Previously developed fluorescence-based tethered approach for probing intermolecular interactions (TAPIN) and AFM-based single-molecule force spectroscopy are capable of probing dimers of Aβ peptides. In this paper, a novel polymer nanoarray approach to probe trimers and tetramers formed by the Aβ(14-23) segment of Aβ protein at the single-molecule level is applied...
June 16, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28621168/detection-of-hb-rothschild-hbb-c-112t-a-or-112t-c-through-high-index-of-suspicion-on-abnormal-pulse-oximetry
#13
Nazeer A Alli, Piet Wessels, Narisha Rampersad, Barnaby E Clark, Swee Lay Thein
We describe a case with a low oxygen affinity hemoglobin (Hb) variant who presented with cyanosis in the absence of cardiopulmonary disease. The patient, a 27-year-old pregnant female (P1G2), complained of a productive cough and bluish discoloration of the lips that started 3 days prior to seeking attention. She had no previous episodes and has generally been in good health. A positive family history of cyanosis was obtained in one sibling. Systematic examination, notably the cardiorespiratory system, revealed no abnormalities...
June 16, 2017: Hemoglobin
https://www.readbyqxmd.com/read/28620653/successive-annual-influenza-vaccination-induces-a-recurrent-oligoclonotypic-memory-response-in-circulating-t-follicular-helper-cells
#14
Ramin Sedaghat Herati, Alexander Muselman, Laura Vella, Bertram Bengsch, Kaela Parkhouse, Daniel Del Alcazar, Jonathan Kotzin, Susan A Doyle, Pablo Tebas, Scott E Hensley, Laura F Su, Kenneth E Schmader, E John Wherry
T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28619510/crystal-structure-of-brlr-with-c-di-gmp
#15
Harikiran Raju, Rohan Sharma
The transcriptional regulator BrlR is a member of the MerR family of multidrug transport activators in Pseudomonas aeruginosa. Recent study indicates that BrlR is a novel 3',5'-cyclic diguanylic acid (c-di-GMP) receptor and can be activated by c-di- GMP. To gain insight into BrlR function, we determined the structure of BrlR with c-di-GMP complex structure to 2.5 Å. The structure and SEC data revealed BrlR forms a tetramer and each BrlR protomer consists of three parts, DNA-binding domain, a coiled-coil region and GyrI-like domain...
June 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28618781/cavity-type-dna-origami-based-plasmonic-nanostructures-for-raman-enhancement
#16
Mengzhen Zhao, Xu Wang, Shaokang Ren, Yikang Xing, Jun Wang, Nan Teng, Dongxia Zhao, Wei Liu, Dan Zhu, Shao Su, Jiye Shi, Shiping Song, Lihua Wang, Jie Chao, Lianhui Wang
DNA origami has been established as addressable templates for site-specific anchoring of gold nanoparticles (AuNPs). Given that AuNPs are assembled by charged DNA oligonucleotides, it is important to reduce the charge repulsion between AuNPs-DNA and the template to realize high yields. Herein, we developed a cavity-type DNA origami as templates to organize 30-nm AuNPs, which formed dimer and tetramer plasmonic nanostructures. Transmission electron microscopy (TEM) images showed that high yields of dimer and tetramer plasmonic nanostructures were obtained by using the cavity-type DNA origami as the template...
June 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28617592/kinetic-and-thermodynamic-analysis-of-acetyl-coa-activation-of-staphylococcus-aureus-pyruvate-carboxylase
#17
Lauren E Westerhold, Lance C Bridges, Saame Raza Shaikh, Tonya Nicole Zeczycki
Allosteric regulation of pyruvate carboxylase (PC) activity is pivotal to maintaining metabolic homeostasis. In contrast, dysregulated PC activity contributes to the pathogenesis of numerous diseases, rendering PC a possible target for allosteric therapeutic development. Recent research efforts have focused on demarcating the role of acetyl-CoA, one of the most potent activators of PC, in coordinating catalytic events within the multifunctional enzyme. Herein, we report a kinetic and thermodynamic analysis of acetyl-CoA activation of the Staphylococcus aureus PC (SaPC) catalyzed carboxylation of pyruvate to identify novel means by which acetyl-CoA synchronizes catalytic events within the PC tetramer...
June 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28615708/epitope-mapping-and-kinetics-of-cd4-t-cell-immunity-to-pneumonia-virus-of-mice-in-the-c57bl-6-strain
#18
Lana Vandersarren, Cedric Bosteels, Manon Vanheerswynghels, James J Moon, Andrew J Easton, Gert Van Isterdael, Sophie Janssens, Bart N Lambrecht, Mary J van Helden
Pneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific T cells in C57BL/6 mice as the majority of transgenic mice are only available on this background. While PVM-specific CD8 T cell epitopes were recently described, so far no PVM-specific CD4 T cell epitopes have been identified within the C57BL/6 strain...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615444/the-human-mitochondrial-single-strand-dna-binding-protein-displays-distinct-kinetics-and-thermodynamics-of-dna-binding-and-exchange
#19
Yufeng Qian, Kenneth A Johnson
The human mitochondrial SSB (mtSSB) is a homo-tetrameric protein, involved in mtDNA replication and maintenance. Although mtSSB is structurally similar to SSB from Escherichia coli (EcoSSB), it lacks the C-terminal disordered domain but little is known about the biophysics of mtSSB-ssDNA interactions. Here, we characterized the kinetics and thermodynamics of mtSSB binding to ssDNA by equilibrium titrations and stopped-flow kinetic measurements. We show that the mtSSB tetramer can bind to ssDNA in two distinct binding modes: (SSB)30 and (SSB)60, defined by DNA binding site sizes of 30 and 60 nt, respectively...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28614718/sirt5-desuccinylates-and-activates-pyruvate-kinase-m2-to-block-macrophage-il-1%C3%AE-production-and-to-prevent-dss-induced-colitis-in-mice
#20
Fang Wang, Ke Wang, Wei Xu, Shimin Zhao, Dan Ye, Yi Wang, Ying Xu, Lisha Zhou, Yiwei Chu, Cuiping Zhang, Xue Qin, Pengyuan Yang, Hongxiu Yu
LPS-activated macrophages undergo a metabolic shift from dependence on mitochondria-produced ATP to reliance on aerobic glycolysis, where PKM2 is a critical determinant. Here, we show that PKM2 is a physiological substrate of SIRT5 and that SIRT5-regulated hypersuccinylation inhibits the pyruvate kinase activity of PKM2 by promoting its tetramer-to-dimer transition. Moreover, a succinylation-mimetic PKM2 K311E mutation promotes nuclear accumulation and increases protein kinase activity. Furthermore, we show that SIRT5-dependent succinylation promotes PKM2 entry into nucleus, where a complex of PKM2-HIF1α is formed at the promoter of IL-1β gene in LPS-stimulated macrophages...
June 13, 2017: Cell Reports
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