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https://www.readbyqxmd.com/read/28088083/specificity-and-stability-of-transient-protein-protein-interactions
#1
REVIEW
Sneha Vishwanath, Anshul Sukhwal, Ramanathan Sowdhamini, Narayanaswamy Srinivasan
Remarkable features that are achieved in a protein-protein complex to precise levels are stability and specificity. Deviation from the normal levels of specificity and stability, which is often caused by mutations, could result in disease conditions. Chemical nature, 3-D arrangement and dynamics of interface residues code for both specificity and stability. This article reviews roles of interfacial residues in transient protein-protein complexes. It is proposed that aside from hotspot residues conferring stability to the complex, a small set of 'rigid' residues at the interface that maintain conformation between complexed and uncomplexed forms, play a major role in conferring specificity...
January 11, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28088061/galectins-emerging-regulatory-checkpoints-linking-tumor-immunity-and-angiogenesis
#2
REVIEW
Santiago P Méndez-Huergo, Ada G Blidner, Gabriel A Rabinovich
Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining immune cell homeostasis, may be co-opted by cancer cells to evade immune destruction. Therapies targeting immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype...
January 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28088012/new-4-4-chlorophenyl-2-2-6-2%C3%A2-terpyridine-ruthenium-ii-complexes-synthesis-characterization-interaction-with-dna-bsa-and-cytotoxicity-studies
#3
Milan M Milutinović, Ana Rilak, Ioannis Bratsos, Olivera Klisurić, Milan Vraneš, Nevenka Gligorijević, Siniša Radulović, Živadin D Bugarčić
In this study, we have developed a series of new monofunctional Ru(II) complexes of the general formula mer-[Ru(Cl-Ph-tpy)(N-N)Cl]Cl in which Cl-Ph-tpy is 4'-(4-chlorophenyl)-2,2':6',2″-terpyridine, N-N is a bidentate chelating ligand (1,2-diaminoethane (en, 1), 1,2-diaminocyclohexane (dach, 2) or 2,2'-bipyridine (bpy, 3)). All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR). Their chemical behavior in aqueous solution was studied by UV-Vis and NMR spectroscopy showing that all compounds are relatively labile leading to the formation of the corresponding aqua species 1aq-3aq...
October 14, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28087981/humanized-chondroitinase-abc-sensitizes-glioblastoma-cells-to-temozolomide
#4
Alena Cristina Jaime-Ramirez, Nina Dmitrieva, Ji Young Yoo, Yeshavanth Banasavadi-Siddegowda, Jianying Zhang, Theresa Relation, Chelsea Bolyard-Blessing, Jeffrey Wojton, Balveen Kaur
INTRODUCTION: Malignant gliomas (GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extra cellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM...
January 14, 2017: Journal of Gene Medicine
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
#5
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/28087810/akt1-lkb1-and-yap1-revealed-as-myc-interactors-with-nanoluc-based-protein-fragment-complementation-assay
#6
Xiu-Lei Mo, Qi Qi, Andrei A Ivanov, Qiankun Niu, Yin Luo, Jonathan Havel, Russell Goetze, Sydney Bell, Carlos S Moreno, Lee A D Cooper, Margaret A Johns, Fadlo R Khuri, Yuhong Du, Haian Fu
The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. Here we report the development of a NanoLuc®-based protein-fragment complementation assay (NanoPCA) and mapping of the MYC protein interaction hub in live mammalian cells. The NanoPCA system was configured to enable detection of protein-protein interactions (PPI) at the endogenous level, as shown with PRAS40 dimerization, and detection of weak interactions, such as PINCH1-NCK2...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087739/tnf-signaling-through-rip1-kinase-enhances-sn38-induced-death-in-colon-adenocarcinoma
#7
Lucia Cabal-Hierro, Peter J O'Dwyer
: Elucidation of tumor necrosis factor (TNF)-directed mechanisms for cell death induction and maintenance of tumor growth has revealed a role for receptor-interacting protein kinases 1 and 3 (RIPK1/RIP1 and RIPK3/RIP3), components of the necrosome complex, as determinants of cell fate. Here the participation of TNF signaling was analyzed with regard to the cytotoxic action of different DNA damaging agents in a panel of colon cancer cells. While most of these cell lines were insensitive to TNF, combination with these drugs increased sensitivity by inducing cell death and DNA damage, especially in the case of the topoisomerase inhibitor SN38...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28087731/increased-nbcn1-expression-na-hco3-co-transport-and-intracellular-ph-in-human-vascular-smooth-muscle-cells-with-a-risk-allele-for-hypertension
#8
Fu Liang Ng, Ebbe Boedtkjer, Katarzyna Witkowska, Meixia Ren, Ruoxin Zhang, Arthur Tucker, Christian Aalkjær, Mark J Caulfield, Shu Ye
Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na(+)/HCO3 co-transporter NBCn1 which regulates intracellular pH (pHi). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allele is associated with increased SLC4A7 expression level, NBCn1 availability and function as reflected in elevated steady-state pHi and accelerated recovery from intracellular acidosis...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#9
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/28087710/targeting-argonaute-to-chromatin
#10
Jered M Wendte, Craig S Pikaard
In many eukaryotes, siRNAs bound to Argonaute proteins guide chromatin-modifying enzymes to complementary loci, resulting in transcriptional gene silencing. Multiple lines of evidence indicate that siRNAs base-pair with longer RNAs produced at target loci, but the possibility that siRNAs base-pair directly with DNA remains an attractive hypothesis. In a recent study, Shimada et al. (pp. 2571-2580) conducted experiments that address these alternative hypotheses, yielding additional evidence that fission yeast siRNA-Argonaute silencing complexes are recruited to target loci exclusively via interactions with nascent transcripts...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087697/development-of-high-affinity-and-high-specificity-inhibitors-of-metalloproteinase-14-through-computational-design-and-directed-evolution
#11
Valeria Arkadash, Gal Yosef, Jason Shirian, Itay Cohen, Yuval Horev, Moran Grossman, Irit Sagi, Evette S Radisky, Julia M Shifman, Niv Papo
Degradation of the extracellular matrices in the human body is controlled by matrix metalloproteinases (MMPs), a family of more than 20 homologous enzymes. Imbalance in MMP activity can result in many diseases, such as arthritis, cardiovascular diseases, neurological disorders, fibrosis, and cancers. Thus, MMPs present attractive targets for drug design and have been a focus for inhibitor design for as long as three decades. Yet, to date, all MMP inhibitors have failed in clinical trials because of their broad activity against numerous MMP family members and the serious side effects of the proposed treatment...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087696/genetic-and-biochemical-characterization-of-a-gene-operon-for-trans-aconitic-acid-a-novel-nematicide-from-bacillus-thuringiensis
#12
Cuiying Du, Shiyun Cao, Xiangyu Shi, Xiangtao Nie, Jinshui Zheng, Yun Deng, Lifang Ruan, Donghai Peng, Ming Sun
Trans-aconitic acid (TAA) is an isomer of cis-aconitic acid (CAA), an intermediate of the tricarboxylic acid (TCA) cycle that is synthesized by aconitase. Although TAA production has been detected in bacteria and plants for many years and is known to be a potent inhibitor of aconitase, its biosynthetic origins and the physiological relevance of its activity have remained unclear. We have serendipitously uncovered key information relevant to both of these questions. Specifically, in a search for novel nematicidal factors from Bacillus thuringiensis, a significant nematode pathogen harboring many protein virulence factors, we discovered a high-yielding component that showed activity against the plant-parasitic nematode Meloidogyne incognita and surprisingly identified it as TAA...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087685/bst-2-restricts-iav-release-and-is-countered-by-the-viral-m2-protein
#13
Siqi Hu, Lijuan Yin, Shan Mei, Jian Li, Fengwen Xu, Hong Sun, Xiaoman Liu, Shan Cen, Chen Liang, Ailing Li, Fei Guo
BST-2 (tetherin, CD317, HM1.24) is induced by interferon and restricts virus release by tethering the enveloped viruses to the cell surface. The effect of BST-2 on influenza A virus (IAV) infection has been inconclusive. In this study, we report that BST-2 diminishes the production of IAV virus-like particles, that are generated by viral NA and HA proteins, to a much greater degree than inhibits the production of wild type IAV particles. This relatively weaker inhibition of IAV is associated with reduction of BST-2 levels, which is caused by the M2 protein that interacts with BST-2 and leads to downregulation of cell surface BST-2 via the proteasomal pathway...
January 13, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28087659/plant-parasitic-nematodes-towards-understanding-molecular-players-in-stress-responses
#14
REVIEW
François-Xavier Gillet, Caroline Bournaud, Jose Dijair Antonino de Souza Júnior, Maria Fatima Grossi-de-Sa
BACKGROUND: Plant-parasitic nematode interactions occur within a vast molecular plant immunity network. Following initial contact with the host plant roots, plant-parasitic nematodes (PPNs) activate basal immune responses. Defence priming involves the release in the apoplast of toxic molecules derived from reactive species or secondary metabolism. In turn, PPNs must overcome the poisonous and stressful environment at the plant-nematode interface. The ability of PPNs to escape this first line of plant immunity is crucial and will determine its virulence...
January 13, 2017: Annals of Botany
https://www.readbyqxmd.com/read/28087654/effects-of-external-strain-on-the-regulation-of-microtubule-sliding-induced-by-outer-arm-dynein-of-sea-urchin-sperm-flagella
#15
Hiroshi Yoke, Chikako Shingyoji
Oscillatory bending movement of eukaryotic flagella is powered by orchestrated activity of dynein motor proteins that hydrolyze ATP and produce microtubule sliding. Although the ATP concentration within a flagellum is kept uniform at a few mmol l(-1) level, sliding activities of dyneins are dynamically coordinated along the flagellum in accordance with the phase of bending waves. Thus, at the organellar level the dynein not only generates force for bending but also modulates its motile activity by responding to bending of the flagellum...
January 13, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28087594/a-human-proteome-array-approach-to-identifying-key-host-proteins-targeted-by-toxoplasma-kinase-rop18
#16
Zhaoshou Yang, Yongheng Hou, Taofang Hao, Hee-Sool Rho, Jun Wan, Yizhao Luan, Xin Gao, Jianping Yao, Aihua Pan, Zhi Xie, Jiang Qian, Wanqin Liao, Heng Zhu, Xingwang Zhou
Toxoplasma kinase ROP18 is a key molecule responsible for the virulence of Toxoplasma gondii; however, the mechanisms by which ROP18 exerts parasite virulence via interaction with host proteins remain limited to a small number of identified substrates. To identify a broader array of ROP18 substrates we successfully purified bioactive mature ROP18 and used it to probe a human proteome array. Sixty-eight new putative host targets were identified. Functional annotation analysis suggested that these proteins have a variety of functions including metabolic process, kinase activity and phosphorylation, cell growth, apoptosis and cell death, and immunity, indicating a pleiotropic role of ROP18 kinase...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28087593/norovirus-mediated-modification-of-the-translational-landscape-via-virus-and-host-induced-cleavage-of-translation-initiation-factors
#17
Edward Emmott, Frederic Sorgeloos, Sarah L Caddy, Surender Vashist, Stanislav Sosnovtsev, Richard Lloyd, Kate Heesom, Nicolas Locker, Ian Goodfellow
Noroviruses produce viral RNAs lacking a 5' cap structure and instead use a virus-encoded VPg protein covalently linked to viral RNA to interact with translation initiation factors and drive viral protein synthesis. Norovirus infection results in the induction of the innate response leading to interferon stimulated gene (ISG) transcription. However the translation of the induced ISG mRNAs is suppressed. A SILAC-based mass spectrometry approach was employed to analyse changes to protein abundance in both whole cell and m7GTP-enriched samples to demonstrate that diminished host mRNA translation correlates with changes to the composition of the eukaryotic initiation factor complex...
January 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28087398/interaction-of-mal-de-r%C3%A3-o-cuarto-virus-fijivirus-genus-proteins-and-identification-of-putative-factors-determining-viroplasm-formation-and-decay
#18
Gabriela Llauger, Luis Alejandro de Haro, Victoria Alfonso, Mariana Del Vas
Mal de Río Cuarto virus (MRCV) is a member of the Fijivirus genus, within the Reoviridae family, that replicates and assembles in cytoplasmic inclusion bodies called viroplasms. In this study, we investigated interactions between ten MRCV proteins by yeast two-hybrid (Y2H) assays and identified interactions of non-structural proteins P6/P6, P9-2/P9-2 and P6/P9-1. P9-1 and P6 are the major and minor components of the viroplasms respectively, whereas P9-2 is an N-glycosylated membrane protein of unknown function...
January 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28087344/up-regulation-of-the-active-form-of-small-gtpase-rab13-promotes-macroautophagy-in-vascular-endothelial-cells
#19
Lu Zhang, Fang Dai, LiuQing Cui, Bo Zhou, YuQi Guo
The importance of macroautophagy (hereafter referred to as autophagy) in vascular endothelial cell (VEC) biology and dysfunction is increasingly recognized, but the molecular mechanisms of autophagy in VECs in the presence of serum are still poorly understood. Previously, we identified pterostilbene as a potent autophagy inducer of VECs in the presence of serum. In this study, we used pterostilbene as a tool to induce VEC autophagy and identified the differentially expressed genes using high-throughput DAN microarray...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087343/calcium-remodeling-in-colorectal-cancer
#20
REVIEW
Carlos Villalobos, Diego Sobradillo, Miriam Hernández-Morales, Lucía Núñez
: Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC...
January 10, 2017: Biochimica et Biophysica Acta
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