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Accessory proteins

Danica E DeGroot, Adam Swank, Russell S Thomas, Mark Strynar, Mi-Young Lee, Paul L Carmichael, Steven O Simmons
The US EPA's ToxCast program is designed to assess chemical perturbations of molecular and cellular endpoints using a variety of high-throughput screening (HTS) assays. However, existing HTS assays have limited or no xenobiotic metabolism which could lead to false positive (chemical is detoxified in vivo) as well as false negative results (chemical is bioactivated in vivo) and thus potential mischaracterization of chemical hazard. To address this challenge, the ten most prevalent human liver cytochrome P450 (CYP) enzymes were introduced into a human cell line (HEK293T) with low endogenous metabolic capacity...
March 16, 2018: Journal of Pharmacological and Toxicological Methods
Yi Wang, Yuanyuan Qian, Qilu Fang, Peng Zhong, Weixin Li, Lintao Wang, Weitao Fu, Yali Zhang, Zheng Xu, Xiaokun Li, Guang Liang
This corrects the article DOI: 10.1038/ncomms13997.
March 19, 2018: Nature Communications
Winston X Yan, Shaorong Chong, Huaibin Zhang, Kira S Makarova, Eugene V Koonin, David R Cheng, David A Scott
Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA-targeting systems identified subtype VI-D, encoding dual HEPN domain-containing Cas13d effectors and putative WYL-domain-containing accessory proteins (WYL1 and WYL-b1 through WYL-b5). The median size of Cas13d proteins is 190 to 300 aa smaller than that of Cas13a-Cas13c...
March 9, 2018: Molecular Cell
Balal Brazvan, Abbas Ebrahimi-Kalan, Kobra Velaei, Ahmad Mehdipour, Zeynab Aliyari Serej, Ayyub Ebrahimi, Mohammad Ghorbani, Omid Cheraghi, Hojjatollah Nozad Charoudeh
The end of linear chromosomes is formed of a special nucleoprotein heterochromatin structure with repetitive TTAGGG sequences called telomere. Telomere length is regulated by a special enzyme called telomerase, a specific DNA polymerase that adds new telomeric sequences to the chromosome ends. Telomerase consists of two parts; the central protein part and the accessory part which is a RNA component transported by the central part. Regulation of telomere length by this enzyme is a multi-stage process. Telomere length elongation is strongly influenced by the level of telomerase and has a strong correlation with the activity of telomerase enzyme...
March 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Guang-Zhe Huang, Mutsuo Taniguchi, Ye-Bo Zhou, Jing-Ji Zhang, Fumino Okutani, Yoshihiro Murata, Masahiro Yamaguchi, Hideto Kaba
The formation of mate recognition memory in mice is associated with neural changes at the reciprocal dendrodendritic synapses between glutamatergic mitral cell (MC) projection neurons and GABAergic granule cell (GC) interneurons in the accessory olfactory bulb (AOB). Although noradrenaline (NA) plays a critical role in the formation of the memory, the mechanism by which it exerts this effect remains unclear. Here we used extracellular field potential and whole-cell patch-clamp recordings to assess the actions of bath-applied NA (10 µM) on the glutamatergic transmission and its plasticity at the MC-to-GC synapse in the AOB...
April 2018: Learning & Memory
Joseph E Pick, Edward B Ziff
A fundamental property of the brain is its ability to modify its function in response to its own activity. This ability for self-modification depends to a large extent on synaptic plasticity. It is now appreciated that for excitatory synapses, a significant part of synaptic plasticity depends upon changes in the post synaptic response to glutamate released from nerve terminals. Modification of the post synaptic response depends, in turn, on changes in the abundances of AMPA receptors in the post synaptic membrane...
March 12, 2018: Molecular and Cellular Neurosciences
A Covarrubias-Pinto, A I Acuña, G Boncompain, E Pápic, P V Burgos, F Perez, M A Castro
Ascorbic acid (Asc) is an antioxidant molecule essential for physiological functions. The concentration of extracellular Asc increases during synaptic transmission and renal reabsorption. These phenomena induce an increase of the Sodium-dependent-Vitamin-C-transporter 2 (SVCT2) at plasma membrane (PM) localization, as we previously demonstrated in neuronal and non-neuronal cells. Hence, the aim of this study was to evaluate intracellular SVCT2 trafficking kinetics in response to Asc. We observed two peaks of SVCT2 localization and function at the PM (at 5-10min, "acute response", and 30-60min, "post-acute response") when cells were incubated with Asc...
March 12, 2018: Free Radical Biology & Medicine
Mimi Gao, Melanie Berghaus, Simone Möbitz, Vitor Schuabb, Nelli Erwin, Marius Herzog, Karin Julius, Christian Sternemann, Roland Winter
For over 50 years, it has been known that the mitosis of eukaryotic cells is inhibited already at high hydrostatic pressure conditions of 30 MPa. This effect has been attributed to the disorganization of microtubules, the main component of the spindle apparatus. However, the structural details of the depolymerization and the origin of the pressure sensitivity have remained elusive. It has also been a puzzle how complex organisms could still successfully inhabit extreme high-pressure environments such as those encountered in the depth of oceans...
March 13, 2018: Biophysical Journal
Juliana Porretti, Guillermo N Dalton, Cintia Massillo, Georgina D Scalise, Paula L Farré, Randolph Elble, Esther N Gerez, Paula Accialini, Ana M Cabanillas, Kevin Gardner, Paola De Luca, Adriana De Siervi
Prostate cancer (PCa) is the most common cancer among men. Metabolic syndrome (MeS) is associated with increased PCa aggressiveness and recurrence. Previously, we proposed C-terminal binding protein 1 (CTBP1), a transcripcional co-repressor, as a molecular link between these two conditions. Notably, CTBP1 depletion decreased PCa growth in MeS mice. The aim of this study was to investigate the molecular mechanisms that explain the link between MeS and PCa mediated by CTBP1. We found that CTBP1 repressed Chloride Channel Accessory 2 (CLCA2) expression in prostate xenografts developed in MeS animals...
March 14, 2018: International Journal of Cancer. Journal International du Cancer
Vinicius A C Abreu, Rafael V Popin, Danillo O Alvarenga, Patricia D C Schaker, Caroline Hoff-Risseti, Alessandro M Varani, Marli F Fiore
Cylindrospermopsis raciborskii is a freshwater cyanobacterial species with increasing bloom reports worldwide that are likely due to factors related to climate change. In addition to the deleterious effects of blooms on aquatic ecosystems, the majority of ecotypes can synthesize toxic secondary metabolites causing public health issues. To overcome the harmful effects of C. raciborskii blooms, it is important to advance knowledge of diversity, genetic variation, and evolutionary processes within populations...
2018: Frontiers in Microbiology
Yi Yu, Su Chen, Xiaoqiang Mo, Jihong Gong, Chenhong Li, Xiaofei Yang
Complexins, binding to assembling soluble NSF-attachment protein receptor (SNARE) complexes, activate Ca2+ triggered exocytosis and clamp spontaneous release in the presynaptic terminal. Functions of complexin are structural dependent and mechanistically distinct. To further understand the functional/structural dependence of complexin, here we show that the accessory and central α-helices of complexin are sufficient in activation of Ca2+ triggered vesicle fusion but not in clamping spontaneous release. Targeting the two α-helices to synaptic vesicle suppresses spontaneous release, thus further emphasizing the importance of curvature membrane localization in clamping function...
2018: Frontiers in Molecular Neuroscience
Richard Hemmi Valente, Fernanda Sakai, José Antonio Portes-Junior, Luciana Godoy Viana, Sylvia Mendes Carneiro, Jonas Perales, Norma Yamanouye
Despite numerous studies concerning morphology and venom production and secretion in the main venom gland (and some data on the accessory gland) of the venom glandular apparatus of Viperidae snakes, the primary duct has been overlooked. We characterized the primary duct of the Bothrops jararaca snake by morphological analysis, immunohistochemistry and proteomics. The duct has a pseudostratified epithelium with secretory columnar cells with vesicles of various electrondensities, as well as mitochondria-rich, dark, basal, and horizontal cells...
March 13, 2018: Toxins
Daniel Sauter, Frank Kirchhoff
HIV-1, the main causative agent of AIDS, and related primate lentiviruses show a striking ability to efficiently replicate throughout the lifetime of an infected host. In addition to their high variability, the acquisition of several accessory genes has enabled these viruses to efficiently evade or counteract seemingly strong antiviral immune responses. The respective viral proteins, i.e. Vif, Vpr, Vpu, Vpx and Nef, show a stunning functional diversity, acting by various mechanisms and targeting a large variety of cellular factors involved in innate and adaptive immunity...
February 23, 2018: Cytokine & Growth Factor Reviews
Mary K Phillips-Jones, Stephen E Harding
In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics-the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins...
March 10, 2018: Biophysical Reviews
Nathalia Mayumi Noda-Nicolau, Jossimara Polettini, Márcia Guimarães da Silva, Morgan R Peltier, Ramkumar Menon
The polybacterial invasion of the amniotic cavity and risk of preterm birth is often due to cervicovaginal bacteria such as genital mycoplasmas (Mycoplasma hominis and Ureaplasma urealyticum) and Gardnerella vaginalis. The most studied biomarker associated with preterm birth is interleukin-6 (IL-6), a pleiotropic cytokine that performs different functions based on classical or trans-signaling mechanisms. This study evaluated the changes in IL-6 and IL-6 function associated accessory molecules by human fetal membranes to determine the functional availability of IL-6 assessment in an in vitro model of polybacterial infection...
March 2, 2018: Journal of Reproductive Immunology
Robert M Dores, Michelle Scuba-Gray, Bridgette McNally, Perry Davis, Akiyoshi Takahashi
Previous studies on bony vertebrate MC2R orthologs (i.e., ray finned fishes, amphibians, reptiles, birds, and mammals) have shown that these MC2R orthologs have an obligatory requirement for interaction with bony vertebrate MRAP1 orthologs to a) allow for the trafficking of the MC2R ortholog to the plasma membrane; and b) to allow activation by ACTH, but not by any MSH-sized ligand. In addition, previous studies have found that co-expression of teleost and mammalian MC4R orthologs with corresponding MRAP2 has positive effects on sensitivity to stimulation by αMSH or ACTH...
March 7, 2018: General and Comparative Endocrinology
Maia Kavanagh Williamson, Naomi Coombes, Florian Juszczak, Marios Athanasopoulos, Mariam B Khan, Thomas R Eykyn, Ushani Srenathan, Leonie S Taams, Julianna Dias Zeidler, Andrea T Da Poian, Hendrik Huthoff
Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT) and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1...
March 7, 2018: Viruses
Benoit Couvigny, Saulius Kulakauskas, Nicolas Pons, Benoit Quinquis, Anne-Laure Abraham, Thierry Meylheuc, Christine Delorme, Pierre Renault, Romain Briandet, Nicolas Lapaque, Eric Guédon
Biofilm formation is crucial for bacterial community development and host colonization by Streptococcus salivarius , a pioneer colonizer and commensal bacterium of the human gastrointestinal tract. This ability to form biofilms depends on bacterial adhesion to host surfaces, and on the intercellular aggregation contributing to biofilm cohesiveness. Many S. salivarius isolates auto-aggregate, an adhesion process mediated by cell surface proteins. To gain an insight into the genetic factors of S. salivarius that dictate host adhesion and biofilm formation, we developed a screening method, based on the differential sedimentation of bacteria in semi-liquid conditions according to their auto-aggregation capacity, which allowed us to identify twelve mutations affecting this auto-aggregation phenotype...
2018: Frontiers in Microbiology
Paula Jáuregui, Nathaniel R Landau
Monocyte-derived macrophages (MDMs) are an important target for HIV-1 despite SAMHD1, a myeloid restriction factor for which HIV-1 lacks a counteracting accessory protein. The antiviral activity of SAMHD1 is modulated by phosphorylation of T592 by cyclin-dependent kinases (CDK). We show that treatment of MDMs with neocarzinostatin, a compound that introduces double strand breaks (DBS) in genomic DNA, results in the decrease of phosphorylated SAMHD1, activating its antiviral activity and blocking HIV-1 infection...
March 7, 2018: Scientific Reports
Jing Shi, Ran Xiong, Tao Zhou, Peiyi Su, Xihe Zhang, Xusheng Qiu, Hongmei Li, Sunan Li, Changqing Yu, Bin Wang, Chan Ding, Thomas E Smithgall, Yong-Hui Zheng
The primate lentiviral accessory protein Nef downregulates CD4 and MHC-I from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison with CD4 and MHC-I. We confirm that Nef excludes Ser5 from HIV-1 virions by downregulating its cell surface expression via similar functional motifs required for CD4-downregulation...
March 7, 2018: Journal of Virology
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