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In vivo protein protein interaction

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https://www.readbyqxmd.com/read/28231276/alterations-in-cellular-pharmacokinetics-and-pharmacodynamics-of-elvitegravir-in-response-to-ethanol-exposure-in-hiv-1-infected-monocytic-u1-cells
#1
Narasimha M Midde, Namita Sinha, Pradeep B Lukka, Bernd Meibohm, Santosh Kumar
Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours...
2017: PloS One
https://www.readbyqxmd.com/read/28230861/ripk3-interactions-with-mlkl-and-camkii-mediate-oligodendrocytes-death-in-the-developing-brain
#2
Yi Qu, Jun Tang, Huiqing Wang, Shiping Li, Fengyan Zhao, Li Zhang, Q Richard Lu, Dezhi Mu
Oligodendrocyte progenitor cells (OPCs) death is a key contributor to cerebral white matter injury (WMI) in the developing brain. A previous study by our group indicated that receptor-interacting proteins (RIPs) are crucial in mediating necroptosis in developing neurons. However, whether this mechanism is involved in OPCs death is unclear. We aimed to explore the mechanisms of RIP-mediated oligodendrocytes (OLs) death in the developing brain. Oligodendrocytes necroptosis was induced by oxygen-glucose deprivation plus caspase inhibitor zVAD treatment (OGD/zVAD) in vitro...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230851/using-hiclip-to-identify-rna-duplexes-that-interact-with-a-specific-rna-binding-protein
#3
Yoichiro Sugimoto, Anob M Chakrabarti, Nicholas M Luscombe, Jernej Ule
The structure of RNA molecules has a critical role in regulating gene expression, largely through influencing their interactions with RNA-binding proteins (RBPs). RNA hybrid and individual-nucleotide resolution UV cross-linking and immunoprecipitation (hiCLIP) is a transcriptome-wide method of monitoring these interactions by identifying RNA duplexes bound by a specific RBP. The hiCLIP protocol consists of the following steps: in vivo cross-linking of RBPs to their bound RNAs; partial RNA digestion and purification of RNA duplexes interacting with the specific RBP using immunoprecipitation; ligation of the two arms of RNA duplexes via a linker; reverse transcription; cDNA library amplification; and finally high-throughput DNA sequencing...
March 2017: Nature Protocols
https://www.readbyqxmd.com/read/28228265/e3-ligase-rnf126-directly-ubiquitinates-frataxin-promoting-its-degradation-identification-of-a-potential-therapeutic-target-for-friedreich-ataxia
#4
Monica Benini, Silvia Fortuni, Ivano Condò, Giulia Alfedi, Florence Malisan, Nicola Toschi, Dario Serio, Damiano Sergio Massaro, Gaetano Arcuri, Roberto Testi, Alessandra Rufini
Friedreich ataxia (FRDA) is a severe genetic neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin. To date, there is no therapy to treat this condition. The amount of residual frataxin critically affects the severity of the disease; thus, attempts to restore physiological frataxin levels are considered therapeutically relevant. Frataxin levels are controlled by the ubiquitin-proteasome system; therefore, inhibition of the frataxin E3 ligase may represent a strategy to achieve an increase in frataxin levels...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28227691/understanding-the-cochlear-implant-environment-by-mapping-perilymph-proteomes-from-different-species
#5
Jonathan C Palmer, Megan S Lord, Jeremy L Pinyon, Andrew K Wise, Nigel H Lovell, Paul M Carter, Ya Lang Enke, Gary D Housley, Rylie A Green, Jonathan C Palmer, Megan S Lord, Jeremy L Pinyon, Andrew K Wise, Nigel H Lovell, Paul M Carter, Ya Lang Enke, Gary D Housley, Rylie A Green, Ya Lang Enke, Rylie A Green, Jonathan C Palmer, Nigel H Lovell, Paul M Carter, Jeremy L Pinyon, Gary D Housley, Andrew K Wise, Megan S Lord
Cochlear implants operate within a bony channel of the cochlea, bathed in a fluid known as the perilymph. The perilymph is a complex fluid containing ions and proteins, which are known to actively interact with metallic electrodes. To improve our understanding of how cochlear implant performance varies in preclinical in vivo studies in comparison to human trials and patient outcomes, the protein composition (or perilymph proteome) is needed. Samples of perilymph were gathered from feline and guinea pig subjects and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to produce proteomes and compare against the recently published human proteome...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225217/proteomic-analysis-of-the-cullin4b-interactome-using-proximity-dependent-biotinylation-in-living-cells
#6
Hailong Zhang, Shupeng Li, Pingting Liu, Frankie H F Lee, Albert H C Wong, Fang Liu
Cullin 4B (CUL4B) mutations have been implicated in mental retardation and dopamine-related behaviors due to disruptions in their interaction with Cullin-RING E3 ligases (CRLs). Thus, further identification of CUL4B substrates can increase the knowledge of protein homeostasis and illuminate the role of CUL4B in neuropsychiatric disease. However, the transient nature of the coupling between CUL4B and its substrates is difficult to detect in vivo using current approaches, thus hampers efforts to investigate functions of CRLs within unperturbed living systems...
February 22, 2017: Proteomics
https://www.readbyqxmd.com/read/28223279/distinct-contributions-of-complement-factors-to-platelet-activation-and-fibrin-formation-in-venous-thrombus-development
#7
Saravanan Subramaniam, Kerstin Jurk, Lukas Hobohm, Sven Jäckel, Mona Saffarzadeh, Kathrin Schwierczek, Philip Wenzel, Florian Langer, Christoph Reinhardt, Wolfram Ruf
Expanding evidence indicates multiple interactions between the hemostatic system and innate immunity and the coagulation and complement cascades. Here we show in a tissue factor (TF)-dependent model of flow restriction-induced venous thrombosis that complement factors (C) make distinct contributions to platelet activation and fibrin deposition. C3-deficiency causes prolonged bleeding, reduced thrombus incidence, thrombus size, fibrin and platelet deposition in the ligated inferior vena cava, and diminished platelet activation in vitro...
February 21, 2017: Blood
https://www.readbyqxmd.com/read/28222740/dibutyryl-camp-attenuates-pulmonary-fibrosis-by-blocking-myofibroblast-differentiation-via-pka-creb-cbp-signaling-in-rats-with-silicosis
#8
Yan Liu, Hong Xu, Yucong Geng, Dingjie Xu, Lijuan Zhang, Yi Yang, Zhongqiu Wei, Bonan Zhang, Shifeng Li, Xuemin Gao, Ruimin Wang, Xianghong Zhang, Darrell Brann, Fang Yang
BACKGROUND: Myofibroblasts play a major role in the synthesis of extracellular matrix (ECM) and the stimulation of these cells is thought to play an important role in the development of silicosis. The present study was undertaken to investigate the anti-fibrotic effects of dibutyryl-cAMP (db-cAMP) on rats induced by silica. METHODS: A HOPE MED 8050 exposure control apparatus was used to create the silicosis model. Rats were randomly divided into 4 groups: 1)controls for 16 w; 2)silicosis for 16 w; 3)db-cAMP pre-treatment; 4) db-cAMP post-treatment...
February 21, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28222617/presynaptic-calmodulin-targets-lessons-from-structural-proteomics
#9
Noa Lipstein, Melanie Göth, Christine Piotrowski, Kevin Pagel, Andrea Sinz, Olaf Jahn
Calmodulin (CaM) is a highly conserved Ca(2+)-binding protein that is exceptionally abundant in the brain. In the presynaptic compartment of neurons, CaM transduces changes in Ca(2+) concentration into the regulation of synaptic transmission dynamics. Areas covered: We review selected literature including published CaM interactor screens and outline established and candidate presynaptic CaM targets. We present a workflow of biochemical and structural proteomic methods that were used to identify and characterize the interactions between CaM and Munc13 proteins...
March 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28220688/the-dnaj-protein-osdja6-negatively-regulates-rice-innate-immunity-to-the-blast-fungus-magnaporthe-oryzae
#10
Xionghui Zhong, Jiuxia Yang, Yanlong Shi, Xuli Wang, Guo-Liang Wang
Rice blast, caused by Magnaporthe oryzae (synonym: Pyricularia oryzae), severely reduces rice production and grain quality. The molecular mechanism of rice resistance to M. oryzae is not fully understood. In the present study, we identified a chaperone DnaJ protein, OsDjA6, that is involved in basal resistance to M. oryzae in rice. The OsDjA6 protein is distributed in the entire rice cell. The expression of OsDjA6 is significantly induced in rice after infection with a compatible isolate. Silencing of OsDjA6 in transgenic rice enhances resistance to M...
February 21, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28220610/comparison-and-analysis-on-the-serum-binding-characteristics-of-aspirin-zinc-complex-and-aspirin
#11
Hua-Xin Zhang, Qun Zhang, Hong-Lin Wang, Li-Wei Li
This study was designed to compare the protein-binding characteristics of aspirin-zinc complex (AZN) with those of aspirin itself. AZN was synthesized and interacted with a model transport protein, human serum albumin (HSA). Three-dimensional fluorescence, ultraviolet-visible and circular dichroism (CD) spectra were used to characterize the interaction of AZN with HSA under physiological conditions. The interaction mechanism was explored using a fluorescence quenching method and thermodynamic calculation. The binding site and binding locality of AZN on HSA were demonstrated using a fluorescence probe technique and Förster non-radiation energy transfer theory...
February 21, 2017: Luminescence: the Journal of Biological and Chemical Luminescence
https://www.readbyqxmd.com/read/28220423/leeix2-interactors-analysis-and-eix-mediated-responses-measurement
#12
Meirav Leibman-Markus, Silvia Schuster, Adi Avni
Plant-pathogen interactions involve a large number of wide regulatory systems, necessary for plant defense responses against pathogen attack. The fungal protein ethylene-inducing xylanase (EIX) elicits defense responses in specific cultivars of tobacco and tomato. The response to EIX is controlled by a single locus encoding for LeEIX2, a leucine-rich-repeat receptor-like-protein (LRR-RLP). As an RLP, LeEIX2 does not possess an obvious cytoplasmic signaling moiety such as a kinase domain. To study LeEIX2 mode of action, it is essential to identify the potential interactors involved after EIX perception...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28220417/steady-state-and-kinetics-based-affinity-determination-in-effector-effector-target-interactions
#13
André Reinhard, Thorsten Nürnberger
Dissecting the functional basis of pathogenicity and resistance in the context of plant innate immunity benefits greatly from detailed knowledge about biomolecular interactions, as both resistance and virulence depend on specific interactions between pathogen and host biomolecules. While in vivo systems provide biological context to host-pathogen interactions, these experiments typically cannot provide quantitative biochemical characterization of biomolecular interactions. However, in many cases, the biological function does not only depend on whether an interaction occurs at all, but rather on the "intensity" of the interaction, as quantified by affinity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28220029/a-novel-inhibitor-of-homeodomain-interacting-protein-kinase-2-mitigates-kidney-fibrosis-through-inhibition-of-the-tgf-%C3%AE-1-smad3-pathway
#14
Ruijie Liu, Bhaskar Das, Wenzhen Xiao, Zhengzhe Li, Huilin Li, Kyung Lee, John Cijiang He
Homeodomain interacting protein kinase 2 (HIPK2) is a critical regulator of multiple profibrotic pathways, including that of TGF-β1/Smad3. Genetic ablation of HIPK2 was shown previously to significantly reduce renal fibrosis in the experimental unilateral ureteral obstruction model and Tg26 mice, a model of HIV-associated nephropathy. To develop specific pharmacologic inhibitors of HIPK2 for antifibrotic therapy, we designed and synthesized small molecule inhibitor compounds on the basis of the predicted structure of HIPK2...
February 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28219986/functional-analysis-of-the-transmembrane-and-cytoplasmic-domains-of-pcdh15a-in-zebrafish-hair-cells
#15
Reo Maeda, Itallia V Pacentine, Timothy Erickson, Teresa Nicolson
Protocadherin 15 (PCDH15) is required for mechanotransduction in sensory hair cells as a component of the tip link. Isoforms of PCDH15 differ in their cytoplasmic domains (CD1, CD2, and CD3), but share the extracellular and transmembrane (TMD) domains, as well as an intracellular domain known as the common region (CR). In heterologous expression systems, both the TMD and CR of PCDH15 have been shown to interact with members of the mechanotransduction complex. The in vivo significance of these protein-protein interaction domains of PCDH15 in hair cells has not been determined...
February 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28219947/phosphorylation-potential-of-drosophila-e-cadherin-intracellular-domain-is-essential-for-development-and-regulating-adherens-junction-biosynthetic-dynamics
#16
Yi-Jiun Chen, Juan Huang, Lynn Huang, Erin Austin, Yang Hong
E-Cadherin intracellular domain contains a highly conserved serine cluster whose phosphorylations are essential for binding to β-Catenin in vitro. In cultured cells phosphorylations of specific serine residues within the cluster are also required for regulating adherens junction (AJ) stability and dynamics. However, much less is known how such phosphorylations of E-Cadherin regulate the AJ formation and dynamics in vivo. In this report we generated an extensive array of Drosophila E-Cadherin (DE-Cad) endogenous knock-in alleles that carry mutations targeting this highly conserved serine cluster...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28219790/subunit-specific-synaptic-delivery-of-ampa-receptors-by-auxiliary-chaperone-proteins-tarp%C3%AE-8-and-gsg1l-in-classical-conditioning
#17
Joyce Keifer, Neeraj K Tiwari, Leah Buse, Zhaoqing Zheng
AMPA receptor (AMPAR) trafficking has emerged as a fundamental concept for understanding mechanisms of learning and memory as well as many neurological disorders. Classical conditioning is a simple and highly conserved form of associative learning. Our studies use an ex vivo brainstem preparation in which to study cellular mechanisms underlying learning during a neural correlate of eyeblink conditioning. Two stages of AMPAR synaptic delivery underlie conditioning utilizing sequential trafficking of GluA1-containing AMPARs early in conditioning followed by replacement with GluA4 subunits later...
February 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28219008/nanoroughness-strongly-impacts-lipid-mobility-in-supported-membranes
#18
Florence Sarah Blachon, Frederic F Harb, Bogdan Munteanu, Agnès Piednoir, Remy Fulcrand, Thierry Charitat, Giovanna Fragneto, Olivier Pierre-Louis, Bernard Tinland, Jean-Paul Rieu
In vivo lipid membranes interact with rough supramolecular structures such as protein clusters and fibrils. How these features whose size ranges from a few nanometers to a few tens of nanometers impact lipid and protein mobility is still investigated. Here, we study supported phospholipid bilayers, a unique biomimetic model, deposited on etched surfaces bearing nanometric corrugations. Surface roughness and mean curvature are carefully characterized by AFM imaging using ultrasharp tips. Neutron specular reflectivity supplements this surface characterization, and indicates that the bilayers follow the large scale corrugations of the substrate...
February 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28218424/p16-ink4a-enhances-the-transcriptional-and-the-apoptotic-functions-of-p53-through-dna-dependent-interaction
#19
Huda H Al-Khalaf, Shreeram C Nallar, Dhananjaya V Kalvakolanu, Abdelilah Aboussekhra
p16(INK4A) and p53 are two important tumor suppressor proteins that play essential roles during cell proliferation and aging through regulating the expression of several genes. Here, we report that p16(INK4A) and p53 co-regulate a plethora of transcripts. Furthermore, both proteins colocalize in the nucleus of human primary skin fibroblasts and breast luminal cells, and form a heteromer whose level increases in response to genotoxic stress as well as aging of human fibroblasts and various mouse organs. CDK4 is also present in this heteromeric complex, which is formed only in the presence of DNA both in vitro using pure recombinant proteins and in vivo...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28216567/wine-flavonoids-in-health-and-disease-prevention
#20
Iva Fernandes, Rosa Pérez-Gregorio, Susana Soares, Nuno Mateus, Victor de Freitas
Wine, and particularly red wine, is a beverage with a great chemical complexity that is in continuous evolution. Chemically, wine is a hydroalcoholic solution (~78% water) that comprises a wide variety of chemical components, including aldehydes, esters, ketones, lipids, minerals, organic acids, phenolics, soluble proteins, sugars and vitamins. Flavonoids constitute a major group of polyphenolic compounds which are directly associated with the organoleptic and health-promoting properties of red wine. However, due to the insufficient epidemiological and in vivo evidences on this subject, the presence of a high number of variables such as human age, metabolism, the presence of alcohol, the complex wine chemistry, and the wide array of in vivo biological effects of these compounds suggest that only cautious conclusions may be drawn from studies focusing on the direct effect of wine and any specific health issue...
February 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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