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In vivo protein protein interaction

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https://www.readbyqxmd.com/read/28092051/sh2-binding-site-protection-assay-a-method-for-identification-of-sh2-domain-interaction-partners-by-exploiting-sh2-mediated-phosphosite-protection
#1
Joshua A Jadwin
Over the last two decades there has been a significant effort in the field to characterize the phosphosite binding specificities of SH2 domains with the goal of deciphering the pY signaling code. Although high throughput studies in various formats using most SH2 domains have collectively provided a rich resource of in vitro SH2-pTyr site specificity maps, this data can only be used approximate what is happening in the cell where protein concentrations and localization are not homogenous, as they are for in vitro experiments...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28091653/trivalent-f-elements-in-human-saliva-a-comprehensive-speciation-study-by-time-resolved-laser-induced-fluorescence-spectroscopy-and-thermodynamic-calculations
#2
Astrid Barkleit, Claudia Wilke, Anne Heller, Thorsten Stumpf, Atsushi Ikeda-Ohno
In the case of oral ingestion of radioactive contaminants, the first contact medium is saliva in the mouth. To gain a first insight into the interaction of radioactive contaminants in human saliva, the speciation of curium (Cm(iii)) and europium (Eu(iii)), i.e., trivalent f-elements, was investigated in different salivary media with time-resolved laser-induced fluorescence spectroscopy (TRLFS). The results indicate that these metal cations are primarily complexed with carbonates and phosphates, forming ternary complexes with a possible stoichiometry of 1 : 1 : 2 (M(iii) : carbonate : phosphate)...
January 16, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28090786/inorganic-nitrite-modulates-mirna-signatures-in-acute-myocardial-in-vivo-ischemia-reperfusion
#3
Ulrike B Hendgen-Cotta, Daniel Messiha, Sonja Esfeld, René Deenen, Tienush Rassaf, Matthias Totzeck
Acute myocardial infarction is the leading cause of mortality in the industrialized world. While it is essential to attempt an early reperfusion of ischemic myocardial territories, reperfusion itself adds damage to the heart, the ischemia-reperfusion (I/R) injury. Particularly the injury resulting from the very first minutes of reperfusion remains incompletely understood. MicroRNAs (miRNAs) are dynamic regulators in I/R injury. Nitric oxide (•NO) signaling, in turn, interacts with miRNA signaling. Our previous investigations showed that •NO signaling in I/R could be modulated by nitrite...
January 16, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28089452/co-folding-of-a-flif-flig-split-domain-forms-the-basis-of-the-ms-c-ring-interface-within-the-bacterial-flagellar-motor
#4
Michael J Lynch, Robert Levenson, Eun A Kim, Ria Sircar, David F Blair, Frederick W Dahlquist, Brian R Crane
The interface between the membrane (MS) and cytoplasmic (C) rings of the bacterial flagellar motor couples torque generation to rotation within the membrane. The structure of the C-terminal helices of the integral membrane protein FliF (FliFC) bound to the N terminal domain of the switch complex protein FliG (FliGN) reveals that FliGN folds around FliFC to produce a topology that closely resembles both the middle and C-terminal domains of FliG. The interface is consistent with solution-state nuclear magnetic resonance, small-angle X-ray scattering, in vivo interaction studies, and cellular motility assays...
December 31, 2016: Structure
https://www.readbyqxmd.com/read/28088582/ripk1-protects-hepatocytes-from-kupffer-cells-mediated-tnf-induced-apoptosis-in-mouse-models-of-pamp-induced-hepatitis
#5
Aveline Filliol, Claire Piquet-Pellorce, Céline Raguénès-Nicol, Sarah Dion, Muhammad Farooq, Catherine Lucas-Clerc, Peter Vandenabeele, Mathieu J M Bertrand, Jacques Le Seyec, Michel Samson
BACKGROUND & AIMS: The severity of liver diseases is exacerbated by the death of hepatocytes, which can be induced by the sensing of Pathogen Associated Molecular Patterns (PAMPs) derived from the gut microbiota. The molecular mechanisms regulating these cell death pathways are poorly documented. In this study, we investigated the role of the Receptor Interacting Protein Kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of PAMP-induced hepatitis...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28087830/recognition-of-the-magnaporthe-oryzae-effector-avr-pia-by-the-decoy-domain-of-the-rice-nlr-immune-receptor-rga5
#6
Diana Ortiz, Karine De Guillen, Stella Cesari, Véronique Chalvon, Jérome Gracy, André Padilla, Thomas Kroj
Nucleotide-binding domain and leucine-rich repeat proteins (NLRs) are important receptors in plant immunity that allow recognition of pathogen effectors. The rice NLR RGA5 recognizes the Magnaporthe oryzae effector AVR-Pia through direct interaction. Here, we gained detailed insights into the molecular and structural bases of AVR-Pia-RGA5 interaction and the role of the RATX1 decoy domain of RGA5. NMR titration combined with in vitro and in vivo protein-protein interaction analyses identified the AVR-Pia interaction surface that binds to the RATX1 domain...
January 13, 2017: Plant Cell
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#7
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28086916/microglial-activation-in-parkinson-s-disease-using-18-f-feppa
#8
Christine Ghadery, Yuko Koshimori, Sarah Coakeley, Madeleine Harris, Pablo Rusjan, Jinhee Kim, Sylvain Houle, Antonio P Strafella
BACKGROUND: Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson's disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo. METHODS: Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [(18)F]-FEPPA between PD patients and HC...
January 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28077657/lmp1-and-lmp2a-collaborate-to-promote-epstein-barr-virus-ebv-induced-b-cell-lymphomas-in-a-cord-blood-humanized-mouse-model-but-are-not-essential
#9
Shi-Dong Ma, Ming-Han Tsai, James C Romero-Masters, Erik A Ranheim, Shane M Huebner, Jillian Bristol, Henri-Jacques Delecluse, Shannon C Kenney
: Epstein-Barr virus (EBV) infection is associated with B cell lymphomas in humans. The ability of EBV to convert human B cells into long-lived lymphoblastoid cell lines (LCLs) in vitro requires the collaborative effects of EBNA2 (which hijacks notch signaling), LMP1 (which mimics CD40 signaling), and EBNA 3A/3C (which inhibit oncogene-induced senescence and apoptosis). However, we recently showed that an LMP1-deleted EBV mutant induces B cell lymphomas in a newly developed cord blood-humanized mouse model that allows EBV-infected B cells to interact with CD4 T cells (the major source of CD40 ligand)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077656/hierarchical-and-redundant-roles-of-activating-fc%C3%AE-rs-in-protection-against-influenza-disease-by-m2e-specific-igg1-and-igg2a-antibodies
#10
Silvie Van den Hoecke, Katrin Ehrhardt, Annasaheb Kolpe, Karim El Bakkouri, Lei Deng, Hendrik Grootaert, Steve Schoonooghe, Anouk Smet, Mostafa Bentahir, Kenny Roose, Michael Schotsaert, Bert Schepens, Nico Callewaert, Falk Nimmerjahn, Peter Staeheli, Hartmut Hengel, Xavier Saelens
: The ectodomain of matrix protein 2 is a universal influenza A vaccine candidate that provides protection through antibody-dependent effector mechanisms. Here we compared the functional engagement of Fcγ Receptor family members by two M2e-specific monoclonal antibodies: mAb 37 (IgG1) and mAb 65 (IgG2a), which recognize a similar epitope in M2e with similar affinity. Binding of mAb 65 to influenza A virus-infected cells triggered all three activating mouse Fcγ receptors in vitro, whereas mAb 37 only activated FcγRIII...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077650/melanin-or-melanin-like-substance-interacts-with-the-n-terminal-portion-of-prion-protein-and-inhibits-abnormal-prion-protein-formation-in-prion-infected-cells
#11
Taichi Hamanaka, Keiko Nishizawa, Yuji Sakasegawa, Ayumi Oguma, Kenta Teruya, Hiroshi Kurahashi, Hideyuki Hara, Suehiro Sakaguchi, Katsumi Doh-Ura
Prion diseases are progressive fatal neurodegenerative illnesses caused by the accumulation of transmissible abnormal prion protein (PrP). To find treatments for prion diseases, we searched for substances from natural resources that inhibit abnormal PrP formation in prion-infected cells. We found that high-molecular-weight components from insect cuticle extracts reduced abnormal PrP levels. The chemical nature of these components was consistent with that of melanin. In fact, synthetic melanin produced from tyrosine or 3-hydroxy-l-tyrosine inhibited abnormal PrP formation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077642/studies-on-the-interaction-of-tumor-derived-hd5-alpha-defensins-with-adenoviruses-and-implications-for-oncolytic-adenovirus-therapy
#12
Charles Vragniau, Jens-Martin Hübner, Peter Beidler, Sucheol Gil, Kamola Saydaminova, Zhuo-Zhuang Lu, Roma Yumul, Hongjie Wang, Maximilian Richter, Pavel Sova, Charles Drescher, Pascal Fender, André Lieber
: Defensins are small anti-microbial peptides capable of neutralizing human adenovirus (HAdV) in vitro by binding capsid proteins and blocking endosomal escape of virus. In humans, the alpha defensin HD5 is produced by specialized epithelial cells of the gastro-intestinal and genito-urinary tracts. Here we demonstrate that HD5 is also expressed as an active, secreted peptide by epithelial ovarian and lung cancer cells in situ, in patient biopsies. This finding triggered us to study the role of HD5 in infection and spread of replication-competent, oncolytic HAdV type 3 virus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077325/role-of-14-3-3-sigma-in-over-expression-of-p-gp-by-rifampin-and-paclitaxel-stimulation-through-interaction-with-pxr
#13
So Won Kim, Md Hasanuzzaman, Munju Cho, Nam Hyun Kim, Hye-Young Choi, Jung Woo Han, Hyun June Park, Ji Won Oh, Jae-Gook Shin
In this study, we presented the role of 14-3-3σ to activate CK2-Hsp90β-PXR-MDR1 pathway on rifampin and paclitaxel treated LS174T cells and in vivo LS174T cell-xenografted nude mouse model. Following several in vitro and in vivo experiments, rifampin and paclitaxel were found to be stimulated the CK2-Hsp90β-PXR-MDR1 pathway. Of the proteins in this pathway, Pregnane X receptor (PXR) is a representative transcription factor of multidrug resistance protein 1 (MDR1). We constructed FLAG-PXR-LS174T stable cell lines and discovered 22 proteins that interacted with PXR on rifampin treatment...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28076792/the-mre11-nbs1-interface-is-essential-for-viability-and-tumor-suppression
#14
Jun Hyun Kim, Malgorzata Grosbart, Roopesh Anand, Claire Wyman, Petr Cejka, John H J Petrini
The Mre11 complex (Mre11, Rad50, and Nbs1) is integral to both DNA repair and ataxia telangiectasia mutated (ATM)-dependent DNA damage signaling. All three Mre11 complex components are essential for viability at the cellular and organismal levels. To delineate essential and non-essential Mre11 complex functions that are mediated by Nbs1, we used TALEN-based genome editing to derive Nbs1 mutant mice (Nbs1(mid) mice), which harbor mutations in the Mre11 interaction domain of Nbs1. Nbs1(mid) alleles that abolished interaction were incompatible with viability...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076326/cytosolic-thumpd1-promotes-breast-cancer-cells-invasion-and-metastasis-via-the-akt-gsk3-snail-pathway
#15
Xiupeng Zhang, Guiyang Jiang, Mingfang Sun, Haijing Zhou, Yuan Miao, Mengyuan Liang, Enhua Wang, Yong Zhang
Human THUMP domain-containing protein 1 (THUMPD1) is a specific adaptor protein that modulates tRNA acetylation through interaction with NAT10. Immunohistochemical analysis of 146 breast cancer specimens (82 triple-negative and 64 non-triple-negative cases) indicated THUMPD1 expression is higher in breast cancer tissues (60.9%, 89/146) than normal breast tissues (28.3%, 15/53; p < 0.001). Overall and cytosolic, but not nuclear, THUMPD1 expression in breast cancer correlated with advanced TNM stage (p = 0...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076321/secretion-modification-region-derived-peptide-blocks-exosome-release-and-mediates-cell-cycle-arrest-in-breast-cancer-cells
#16
Ming-Bo Huang, Ruben R Gonzalez, James Lillard, Vincent C Bond
PURPOSE: Discovery and development of a novel anticancer PEG-SMR-Clu peptide to prevent breast cancer metastasis. How breast cancer cells and primary mammary epithelial cells interact and communicate with each other to promote tumorigenesis and how to prevent tumor metastasis has long been a concern of researchers. Cancer cells secrete exosomes containing proteins and RNA. These factors can influence tumor development by directly targeting cancer cells and tumor stroma. In this study, we determined the effects of a peptide as an inhibitor of exosome secretion on breast tumors...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075463/expression-of-the-promyelocytic-leukemia-protein-without-the-nuclear-localization-signal-as-a-novel-diagnostic-marker-for-acute-promyelocytic-leukemia
#17
Ting Xu, Xiao-Qun Yang, Kai-Ling Jiang, Hui Wang, Peng-Peng Ma, Liang Zhong, Bei-Zhong Liu
Promyelocytic leukemia-retinoic acid receptor α (PML-RARα) is a fusion protein generated by the t(15;17)(q22;q12) translocation associated with acute promyelocytic leukemia (APL). PML-RARα is cleaved by neutrophil elastase, an early myeloid-specific serine protease, leading to translocation of the nuclear localization signal (NLS) of the PML protein to the N-terminal of RARα, and the mutational product PML(NLS-). The present study was designed to analyze the role of the NLS in mediating PML transport into the nucleus and to evaluate the value of measuring NLS translocation in the early diagnosis of APL...
January 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28073784/platelets-and-neutrophil-extracellular-traps-collaborate-to-promote-intravascular-coagulation-during-sepsis-in-mice
#18
Braedon McDonald, Rachelle P Davis, Seok-Joo Kim, Mandy Tse, Charles T Esmon, Elzbieta Kolaczkowska, Craig N Jenne
Neutrophil extracellular traps (NETs; webs of DNA coated in anti-microbial proteins) are released into the vasculature during sepsis where they contribute to host defense, but also cause tissue damage and organ dysfunction. Various components of NETs have also been implicated as activators of coagulation. Using multi-color confocal intravital microscopy in mouse models of sepsis, we observed profound platelet aggregation, thrombin activation, and fibrin clot formation within (and downstream of) NETs in vivo...
January 10, 2017: Blood
https://www.readbyqxmd.com/read/28072536/role-of-ionic-strength-and-ph-in-modulating-thermodynamic-profiles-associated-with-co-escape-from-rice-nonsymbiotic-hemoglobin-1
#19
David Butcher, Sophie Bernad, Valerie Derrien, Pierre Sebban, Jaroslava Miksovska
Type 1 nonsymbiotic hemoglobins are found in a wide variety of land plants and exhibit very high affinities for exogenous gaseous ligands. These proteins are presumed to have a role in protecting plant cells from oxidative stress under etiolated/hypoxic conditions through NO dioxygenase activity. In this study we have employed photoacoustic calorimetry, time-resolved absorption spectroscopy, and classical molecular dynamics simulations in order to elucidate thermodynamics, kinetics, and ligand migration pathways upon CO photodissociation from WT and a H73L mutant of type 1 nonsymbiotic hemoglobin from Oryza sativa (rice)...
January 10, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28071726/the-ppe2-protein-of-mycobacterium-tuberculosis-translocates-to-host-nucleus-and-inhibits-nitric-oxide-production
#20
Khalid Hussain Bhat, Shruti Srivastava, Sandeep Kumar Kotturu, Sudip Ghosh, Sangita Mukhopadhyay
Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. It has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. Here, we show that one of the unique PPE family member proteins of M. tuberculosis, PPE2, can limit nitric oxide (NO) production by inhibiting inos gene transcription. PPE2 protein has a leucine zipper DNA-binding motif and a functional nuclear localization signal...
January 10, 2017: Scientific Reports
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