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protein interaction

Gilles Maussion, Cristiana Cruceanu, Jill A Rosenfeld, Scott C Bell, Fabrice Jollant, Jin Szatkiewicz, Ryan L Collins, Carrie Hanscom, Ilaria Kolobova, Nicolas Menjot de Champfleur, Ian Blumenthal, Colby Chiang, Vanessa Ota, Christina Hultman, Colm O'Dushlaine, Steve McCarroll, Martin Alda, Sebastien Jacquemont, Zehra Ordulu, Christian R Marshall, Melissa T Carter, Lisa G Shaffer, Pamela Sklar, Santhosh Girirajan, Cynthia C Morton, James F Gusella, Gustavo Turecki, Dimitri J Stavropoulos, Patrick F Sullivan, Stephen W Scherer, Michael E Talkowski, Carl Ernst
We performed whole-genome sequencing on an individual from a family with variable psychiatric phenotypes that had a sensory processing disorder, apraxia, and autism. The proband harbored a maternally inherited balanced translocation (46,XY,t(11;14)(p12;p12)mat) that disrupted LRRC4C, a member of the highly specialized netrin G family of axon guidance molecules. The proband also inherited a paternally derived chromosomal inversion that disrupted DPP6, a potassium channel interacting protein. Copy Number (CN) analysis in 14,077 cases with neurodevelopmental disorders and 8,960 control subjects revealed that 60% of cases with exonic deletions in LRRC4C had a second clinically recognizable syndrome associated with variable clinical phenotypes, including 16p11...
October 19, 2016: American Journal of Medical Genetics. Part A
Buki Kwon, Palinda Ruvan Munashingha, Yong-Keol Shin, Chul-Hwan Lee, Bing Li, Yeon-Soo Seo
Highly conserved eukaryotic histones are polybasic proteins that package DNA into nucleosomes, a building block of chromatin, allowing extremely long DNA molecules to form compact and discrete chromosomes. The histone N-terminal tails that extend from the nucleosome core act as docking sites for many proteins through diverse posttranslational modifications, regulating various DNA transactions. In this report, we present evidence that the nucleosomes can positively regulate the enzymatic activity of Rad27 (yeast Fen1), a major processing enzyme important for Okazaki fragment in eukaryotes...
October 19, 2016: FEBS Journal
Valeria Lanza, Alessio Travaglia, Gaetano Malgieri, Roberto Fattorusso, Giuseppe Grasso, Giuseppe Di Natale, Valeria Zito, Giuseppe Arena, Danilo Milardi, Enrico Rizzarelli
Many biochemical pathways involving nerve growth factor (NGF), a neurotrophin with copper(II) binding abilities, are regulated by the ubiquitin (Ub) proteasome system. However, whether NGF binds Ub and the role played by copper(II) ions in modulating their interactions have not yet been investigated. Herein NMR spectroscopy, circular dichroism, ESI-MS, and titration calorimetry are employed to characterize the interactions of NGF with Ub. NGF1-14 , which is a short model peptide encompassing the first 14 N-terminal residues of NGF, binds the copper-binding regions of Ub (KD =8...
October 19, 2016: Chemistry: a European Journal
Sharon L I Wong, Maria B Sukkar
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein which regulates interactions between cells and their surrounding extracellular matrix (ECM), and thus governs fundamental cellular functions such as cell adhesion, proliferation and differentiation. SPARC also regulates the expression and activity of numerous growth factors and matrix metalloproteinases essential for ECM degradation and turnover. Studies in SPARC-null mice have revealed a critical role for SPARC in tissue development, injury and repair, and in the regulation of the immune response...
October 19, 2016: British Journal of Pharmacology
Rebba C Boswell-Casteel, Franklin A Hays
Equilibrative nucleoside transporters (ENTs) are polytopic integral membrane proteins that mediate the transport of nucleosides, nucleobases, and therapeutic analogs. The best-characterized ENTs are the human transporters hENT1 and hENT2. However, non-mammalian eukaryotic ENTs have also been studied (e.g., yeast, parasitic protozoa). ENTs are major pharmaceutical targets responsible for modulating the efficacy of more than 30 approved drugs. However, the molecular mechanisms and chemical determinants of ENT-mediated substrate recognition, binding, inhibition, and transport are poorly understood...
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
Alberto Baggioli, Carlo A Cavallotti, Antonino Famulari
From proteins and peptides to semiconducting polymers, aliphatic chains on aromatic groups are recurring motifs in macromolecules from very diverse application fields. Fields in which molecular folding and packing determine the macroscopic physical properties that make such advanced materials appealing in the first place. Within each macromolecule, the intrinsic structure of each unit defines how it interacts with its neighbours, ultimately opening up or denying certain backbone conformations. This eventually also determines how macromolecules interact with each other...
October 18, 2016: Physical Chemistry Chemical Physics: PCCP
Karan Kapoor, Michael R Duff, Amit Upadhyay, Joel C Bucci, Arnold M Saxton, Robert J Hinde, Elizabeth E Howell, Jerome Yves Baudry
The dynamics of anion-quadrupole (or anion-) interactions formed between negatively charged (Asp/Glu) and aromatic (Phe) side chains are for the first time computationally characterized in RmlC (PDB: 1EP0), a homodimeric epimerase. Empirical force field-based molecular dynamics simulations predict anion-quadrupole pairs and triplets (anion-anion-anion--) are formed by the protein during the simulated trajectory which suggests that the anion-quadrupole interactions may provide a significant contribution to the overall stability of the protein, with an average of -1...
October 18, 2016: Biochemistry
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia...
October 18, 2016: Journal of Pineal Research
Anna Yu Alekseeva, Larisa V Kameneva, Svetlana V Kostyuk, Natalia N Veiko
Oxidized cell-free DNA acts as a stress signal molecule and triggers an adaptive response in human cells. Various membrane DNA recognizing receptors are known as potential sensors for such DNA fragments. In order to clarify which of these sensors are able to interact with cfDNA fragments, circulating in human blood flow in heath and disease, we studied the influence of various cfDNA types on endothelial cells. We incubated these fragments at a physiologically optimal concentration with HUVEC cells for 3-24 h and detected the expression of either TLR9 or AIM2, RIG1 and STING receptors at mRNA and protein levels...
2016: Advances in Experimental Medicine and Biology
Stefan Holdenrieder
Liquid profiling is a traditional concept in laboratory diagnostics using patterns of blood-derived biochemical molecules for disease detection and characterization. Beyond protein and cellular parameters, molecular biomarkers at the DNA, RNA and miRNA level have been developed as promising diagnostic tools in metabolic and malignant diseases as new technologies for ultrasensitive profiling of nucleic acids in blood and body fluids became available. In cancer disease, they are successfully applied for the stratification of patients for individually tailored therapies, treatment monitoring and the sensitive detection of minimal residual disease...
2016: Advances in Experimental Medicine and Biology
Ahmad Bani-Jaber, Iyad Alshawabkeh, Samaa Abdullah, Imad Hamdan, Adel Ardakani, Maha Habash
Due to its unique properties, such as biodegradability, biocompatibility, high amphiphilic property, and micelle formation, casein (CS) has been increasingly studied for drug delivery. We used CS as a drug carrier in solid dispersions (SDs) and evaluated the effect of its degradation by trypsin on drug dissolution from the dispersions. SDs of CS and mefenamic acid (MA) were prepared by physical mixing, kneading, and coprecipitation methods. In comparison to pure MA, the dispersions were evaluated for drug-protein interaction, loss of drug crystalinity, and drug morphology by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy...
October 17, 2016: AAPS PharmSciTech
Ching-Hao Li, Chen-Wei Liu, Chi-Hao Tsai, Yi-Jen Peng, Yu-Hsuan Yang, Po-Lin Liao, Chen-Chen Lee, Yu-Wen Cheng, Jaw-Jou Kang
Aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, has been studied extensively in carcinogenesis through the genomic pathway. In recent years, AHR has also been reported to exert positive or negative effects on epithelial-mesenchymal transition (EMT), the crucial step in tumor malignant progression. However, the detailed mechanism remains controversial. Analysis of AHR-expression levels in non-small cell lung cancer cell lines and lung cancer tissues revealed an inverse correlation between AHR protein levels and tumor cell invasion and metastasis...
October 17, 2016: Archives of Toxicology
Kamalakshi Deka, Archana Singh, Surajit Chakraborty, Rupak Mukhopadhyay, Sougata Saha
ATE1-mediated post-translational addition of arginine to a protein has been shown to regulate activity, interaction, and stability of the protein substrates. Arginylation has been linked to many different stress conditions, namely ER stress, cytosolic misfolded protein stress, and nitrosative stress. However, clear understanding about the effect of arginylation in cellular stress responses is yet to emerge. In this study, we investigated the role of arginylation in heat-stress response. Our findings suggest that Ate1 knock out (KO) cells are more susceptible to heat stress compared with its wild-type counterparts due to the induction of apoptosis in KO cells...
2016: Cell Death Discovery
Alexey L Chernobrovkin, Roman A Zubarev
While the focus of attempts to classify cell death programs has finally shifted in 2010s from microscopy-based morphological characteristics to biochemical assays, more recent discoveries have put the underlying assumptions of many such assays under severe stress, mostly because of the limited specificity of the assays. On the other hand, proteomics can quantitatively measure the abundances of thousands of proteins in a single experiment. Thus proteomics could develop a modern alternative to both semiquantitative morphology assessment as well as single-molecule biochemical assays...
2016: Cell Death Discovery
C-Y Lin, T-W Chang, W-H Hsieh, M-C Hung, I-H Lin, S-C Lai, Y-J Tzeng
Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1...
2016: Cell Death Discovery
Angel R de Lera, A Ganesan
The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders...
2016: Clinical Epigenetics
Drew D Kiraly, Deena M Walker, Erin S Calipari, Benoit Labonte, Orna Issler, Catherine J Pena, Efrain A Ribeiro, Scott J Russo, Eric J Nestler
Addiction to cocaine and other psychostimulants represents a major public health crisis. The development and persistence of addictive behaviors comes from a complex interaction of genes and environment - the precise mechanisms of which remain elusive. In recent years a surge of evidence has suggested that the gut microbiome can have tremendous impact on behavioral via the microbiota-gut-brain axis. In this study we characterized the influence of the gut microbiota on cocaine-mediated behaviors. Groups of mice were treated with a prolonged course of non-absorbable antibiotics via the drinking water, which resulted in a substantial reduction of gut bacteria...
October 18, 2016: Scientific Reports
Masaaki Sugiyama, Hirokazu Yagi, Kentaro Ishii, Lionel Porcar, Anne Martel, Katsuaki Oyama, Masanori Noda, Yasuhiro Yunoki, Reiko Murakami, Rintaro Inoue, Nobuhiro Sato, Yojiro Oba, Kazuki Terauchi, Susumu Uchiyama, Koichi Kato
The molecular machinery of the cyanobacterial circadian clock consists of three proteins: KaiA, KaiB, and KaiC. Through interactions among the three Kai proteins, the phosphorylation states of KaiC generate circadian oscillations in vitro in the presence of ATP. Here, we characterized the complex formation between KaiB and KaiC using a phospho-mimicking mutant of KaiC, which had an aspartate substitution at the Ser431 phosphorylation site and exhibited optimal binding to KaiB. Mass-spectrometric titration data showed that the proteins formed a complex exclusively in a 6:6 stoichiometry, indicating that KaiB bound to the KaiC hexamer with strong positive cooperativity...
October 18, 2016: Scientific Reports
Younho Han, Chae Yul Kim, Heesun Cheong, Kwang Youl Lee
Osterix is a novel bone-related transcription factor involved in osteoblast differentiation, and bone maturation. Because a reciprocal relationship exists between adipocyte and osteoblast differentiation of bone marrow derived mesenchymal stem cells, we hypothesized that Osterix might have a role in adipogenesis. Ablation of Osterix enhanced adipogenesis in 3T3-L1 cells, whereas overexpression suppressed this process and inhibited the expression of adipogenic markers including CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ)...
October 18, 2016: Scientific Reports
Dirk Fahrenkamp, Jinyu Li, Sabrina Ernst, Hildegard Schmitz-Van de Leur, Nicolas Chatain, Andrea Küster, Steffen Koschmieder, Bernhard Lüscher, Giulia Rossetti, Gerhard Müller-Newen
STAT5 is an essential transcription factor in hematopoiesis, which is activated through tyrosine phosphorylation in response to cytokine stimulation. Constitutive activation of STAT5 is a hallmark of myeloid and lymphoblastic leukemia. Using homology modeling and molecular dynamics simulations, a model of the STAT5 phosphotyrosine-SH2 domain interface was generated providing first structural information on the activated STAT5 dimer including a sequence, for which no structural information is available for any of the STAT proteins...
October 18, 2016: Scientific Reports
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