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protein stability

Jiang He, Yuzu Zhao, Erhu Zhao, Xianxing Wang, Zhen Dong, Yibiao Chen, Liqun Yang, Hongjuan Cui
Background: The cancer-testis specific gene Opa interacting protein 5 (OIP5) is a testis-specific gene that is reactivated in many human cancers, but its functions in glioblastoma remain unclear. Here, we assessed the significance of OIP5 in the tumorigenesis and metastasis of glioblastoma for the first time. Methods: An immunohistochemistry assay was performed to detect OIP5 expression changes in glioblastoma patients. Overall survival analysis was performed to evaluate the prognostic significance of OIP5...
March 14, 2018: Neuro-oncology
Jing Wen, Ruitu Lv, Honghui Ma, Hongjie Shen, Chenxi He, Jiahua Wang, Fangfang Jiao, Hang Liu, Pengyuan Yang, Li Tan, Fei Lan, Yujiang Geno Shi, Chuan He, Yang Shi, Jianbo Diao
N6 -methyladenosine (m6 A) is an abundant modification in eukaryotic mRNA, regulating mRNA dynamics by influencing mRNA stability, splicing, export, and translation. However, the precise m6 A regulating machinery still remains incompletely understood. Here we demonstrate that ZC3H13, a zinc-finger protein, plays an important role in modulating RNA m6 A methylation in the nucleus. We show that knockdown of Zc3h13 in mouse embryonic stem cell significantly decreases global m6 A level on mRNA. Upon Zc3h13 knockdown, a great majority of WTAP, Virilizer, and Hakai translocate to the cytoplasm, suggesting that Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-Virilizer-Hakai complex, which is important for RNA m6 A methylation...
March 15, 2018: Molecular Cell
Julia K Nussbacher, Gene W Yeo
RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced UV crosslinking followed by immunoprecipitation (eCLIP) datasets for 126 RBPs to discover miR-encoding genomic loci that are statistically enriched for RBP binding. We find that 92% of RBPs interact directly with at least one miR locus, and that some interactions are cell line specific despite expression of the miR locus in both cell lines evaluated...
March 15, 2018: Molecular Cell
Amporn Suphatrakul, Thaneeya Duangchinda, Natapong Jupatanakul, Kanjanawadee Prasittisa, Suppachoke Onnome, Jutharat Pengon, Bunpote Siridechadilok
Reporter virus is a versatile tool to visualize and to analyze virus infections. However, for flaviviruses, it is difficult to maintain the inserted reporter genes on the viral genome, limiting its use in several studies that require homogeneous virus particles and several rounds of virus replication. Here, we showed that flanking inserted GFP genes on both sides with ribosome-skipping 2A sequences improved the stability and the consistency of their fluorescent signals for dengue-virus-serotype 2 (DENV2) reporter viruses...
2018: PloS One
Zanxia Cao, Yunqiang Bian, Guodong Hu, Liling Zhao, Zhenzhen Kong, Yuedong Yang, Jihua Wang, Yaoqi Zhou
Thermodynamics of the permeation of amino acids from water to lipid bilayers is an important first step for understanding the mechanism of cell-permeating peptides and the thermodynamics of membrane protein structure and stability. In this work, we employed bias-exchange metadynamics simulations to simulate the membrane permeation of all 20 amino acids from water to the center of a dipalmitoylphosphatidylcholine (DPPC) membrane (consists of 256 lipids) by using both directional and torsion angles for conformational sampling...
March 16, 2018: International Journal of Molecular Sciences
N De Neve, B Vlaeminck, F Gadeyne, E Claeys, P Van der Meeren, V Fievez
Previously, polyunsaturated fatty acids (PUFA) from linseed oil were effectively protected (>80%) against biohydrogenation through polyphenol-oxidase-mediated protein crosslinking of an emulsion, prepared with polyphenol oxidase (PPO) extract from potato tuber peelings. However, until now, emulsions of only 2 wt% oil have been successfully protected, which implies serious limitations both from a research perspective (e.g. in vivo trials) as well as for further upscaling toward practical applications. Therefore, the aim of this study was to increase the oil/PPO ratio...
March 16, 2018: Animal: An International Journal of Animal Bioscience
Maud Martin, Alexandra Veloso, Jingchao Wu, Eugene A Katrukha, Anna Akhmanova
Microtubules control different aspects of cell polarization. In cells with a radial microtubule system, a pivotal role in setting up asymmetry is attributed to the relative positioning of the centrosome and the nucleus. Here, we show that centrosome loss had no effect on the ability of endothelial cells to polarize and move in 2D and 3D environments. In contrast, non-centrosomal microtubules stabilized by the microtubule minus-end-binding protein CAMSAP2 were required for directional migration on 2D substrates and for the establishment of polarized cell morphology in soft 3D matrices...
March 16, 2018: ELife
Ramiro Manzano Núñez, James Alejandro Zapata, Herney A García-Perdomo, Diego A Gomez, Mónica A Solís Velasco
INTRODUCTION: Few reports are available about perinatal dengue, with controversial results in regards the risk of perinatal outcome. OBJECTIVE: To report a case of perinatal dengue as a differential diagno sis with neonatal sepsis, which must be considered in endemic areas. CLINICAL CASE: Male newborn of a 23 year-old female, who presented a Non-Structural Protein 1 (NS1) antigen positive to dengue at 36 weeks of gestation and negative anti-dengue antibodies...
December 2017: Revista Chilena de Pediatría
Harmanpreet Singh, Chateshwar Kumar, Narpinder Singh, Surinder Paul, Subheet Kumar Jain
Docosahexaenoic acid (DHA) is a vital structural component of neuronal tissue, which is critically required during pre- and post-natal brain development. Its liquid nature, fishy odor, poor bioavailability and oxidative stability are the major challenges in the development of a pharmaceutically elegant and stable formulation. In the present study, nanocapsules of DHA from microalgae oil were prepared using different combinations of wall materials (carbohydrates, polymers, gum and proteins). The encapsulation using spray drying was done to prepare a pharmaceutically stable DHA formulation...
March 16, 2018: Food & Function
Chye Soi Moi, Chia Kin Yen, Khuen Yen Ng, Koh Rhun Yian
Protein misfolding and aggregation have been considered the common pathological hallmarks for a number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). These abnormal proteins aggregation damage mitochondria and induce oxidative stress and resulting neuronal cell death. Prolong neuronal damage activates microglia and astrocytes, development of inflammation reaction and further promotes neurodegeneration. Thus, elimination of abnormal proteins aggregation without eliciting any adverse effects are the main treatment strategies...
March 15, 2018: CNS & Neurological Disorders Drug Targets
Sunandan Mukherjee, Chandran Nithin, Yasaswi Divakaruni, Ranjit Prasad Bahadur
We dissect the protein-protein interfaces into water preservation (WP), water hydration (WH) and water dehydration (WD) sites by comparing the water mediated hydrogen bonds (H-bond) in the bound and unbound states of the interacting subunits. Upon subunit complexation, if a H-bond between an interface water and a protein polar group is retained, we assign it as WP site; if it is lost, we assign it as WD site and if a new H-bond is created, we assign it as WH site. We find that the density of WD sites is highest followed by WH and WP sites except in antigen and (or) antibody complexes, where the density of WH sites is highest followed by WD and WP sites...
March 16, 2018: Journal of Biomolecular Structure & Dynamics
Caitlin M Davis, Martin Gruebele
Qualitative imaging of biomolecular localization and distribution inside cells has revolutionized cell biology. Most of these powerful techniques require modifications to the target biomolecule. Over the past 10 years, these techniques have been extended to quantitative measurements, from in-cell protein folding rates, to complex dissociation constants, to RNA lifetimes. Such measurements can be affected even when a target molecules is just mildly perturbed by its labels. Here, the impact of labeling on protein (and RNA) structure, stability, and function in cells are discussed via practical examples from recent literature...
March 16, 2018: Biochemistry
Kyle I Mentkowski, Jonathan D Snitzer, Sarah Rusnak, Jennifer K Lang
Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of "cell-free, cell therapy" for cancer, immune disorders, and more recently cardiovascular disease...
March 15, 2018: AAPS Journal
Ayori Mitsutake, Hiroshi Takano
Molecular dynamics simulation is a powerful method for investigating the structural stability, dynamics, and function of biopolymers at the atomic level. In recent years, it has become possible to perform simulations on time scales of the order of milliseconds using special hardware. However, it is necessary to derive the important factors contributing to structural change or function from the complicated movements of biopolymers obtained from long simulations. Although some analysis methods for protein systems have been developed using increasing simulation times, many of these methods are static in nature (i...
March 15, 2018: Biophysical Reviews
Ariel Talavera, Jelle Hendrix, Wim Versées, Dukas Jurėnas, Katleen Van Nerom, Niels Vandenberk, Ranjan Kumar Singh, Albert Konijnenberg, Steven De Gieter, Daniel Castro-Roa, Anders Barth, Henri De Greve, Frank Sobott, Johan Hofkens, Nikolay Zenkin, Remy Loris, Abel Garcia-Pino
Bacterial protein synthesis is intricately connected to metabolic rate. One of the ways in which bacteria respond to environmental stress is through posttranslational modifications of translation factors. Translation elongation factor Tu (EF-Tu) is methylated and phosphorylated in response to nutrient starvation upon entering stationary phase, and its phosphorylation is a crucial step in the pathway toward sporulation. We analyze how phosphorylation leads to inactivation of Escherichia coli EF-Tu. We provide structural and biophysical evidence that phosphorylation of EF-Tu at T382 acts as an efficient switch that turns off protein synthesis by decoupling nucleotide binding from the EF-Tu conformational cycle...
March 2018: Science Advances
Yuan-Jun Xia, Hong Xia, Ling Chen, Qing-Shui Ying, Xiang Yu, Li-Hua Li, Jian-Hua Wang, Ying Zhang
Bone morphogenetic protein-2 (BMP-2) serves an important role in the development of bone and cartilage. However, administration of BMP-2 protein alone by intravenous delivery is not very effective. Sustained delivery of stabilized BMP-2 by carriers has been proven necessary to improve the osteogenesis effect of BMP-2. The present study constructed a novel drug delivery system using dextran sulfate (DS)-chitosan (CS) microspheres and investigated the efficiency of the delivery system on recombinant human bone morphogenetic protein (rhBMP-2)...
April 2018: Experimental and Therapeutic Medicine
Peter L Cummins, Babu Kannappan, Jill E Gready
The ubiquitous enzyme Ribulose 1,5-bisphosphate carboxylase-oxygenase (RuBisCO) fixes atmospheric carbon dioxide within the Calvin-Benson cycle that is utilized by most photosynthetic organisms. Despite this central role, RuBisCO's efficiency surprisingly struggles, with both a very slow turnover rate to products and also impaired substrate specificity, features that have long been an enigma as it would be assumed that its efficiency was under strong evolutionary pressure. RuBisCO's substrate specificity is compromised as it catalyzes a side-fixation reaction with atmospheric oxygen; empirical kinetic results show a trend to tradeoff between relative specificity and low catalytic turnover rate...
2018: Frontiers in Plant Science
Seow Theng Ong, Madhavi Latha Somaraju Chalasani, M H U Turabe Fazil, Praseetha Prasannan, Atish Kizhakeyil, Graham D Wright, Dermot Kelleher, Navin Kumar Verma
Centrosome- and Golgi-localized protein kinase N-associated protein (CG-NAP), also known as AKAP450, is a cytosolic scaffolding protein involved in the targeted positioning of multiple signaling molecules, which are critical for cellular functioning. Here, we show that CG-NAP is predominantly expressed in human primary T-lymphocytes, localizes in close proximity (<0.2 μm) with centrosomal and Golgi structures and serves as a docking platform for Protein Kinase A (PKA). GapmeR-mediated knockdown of CG-NAP inhibits LFA-1-induced T-cell migration and impairs T-cell chemotaxis toward the chemokine SDF-1α...
2018: Frontiers in Immunology
Danuta Gutowska-Owsiak, Jorge Bernardino de La Serna, Marco Fritzsche, Aishath Naeem, Ewa I Podobas, Michael Leeming, Huw Colin-York, Ryan O'Shaughnessy, Christian Eggeling, Graham S Ogg
Epidermal stratification critically depends on keratinocyte differentiation and programmed death by cornification, leading to formation of a protective skin barrier. Cornification is dynamically controlled by the protein filaggrin, rapidly released from keratohyalin granules (KHGs). However, the mechanisms of cornification largely remain elusive, partly due to limitations of the observation techniques employed to study filaggrin organization in keratinocytes. Moreover, while the abundance of keratins within KHGs has been well described, it is not clear whether actin also contributes to their formation or fate...
March 15, 2018: Cell Death & Disease
Alina Fedoseienko, Melinde Wijers, Justina C Wolters, Daphne Dekker, Marieke Smit, Nicolette Huijkman, Niels Kloosterhuis, Helene Klug, Aloys Schepers, Ko Willems van Dijk, Johannes H Levels, Daniel D Billadeau, Marten H Hofker, Jan van Deursen, Marit Westerterp, Ezra Burstein, Jan Albert Kuivenhoven, Bart van de Sluis
<u>Rationale:</u> <u>CO</u> pper<u>M</u>etabolism<u>M</u>URR1 Domain-containing (COMMD) proteins are a part of the COMMD-CCDC22-CCDC93 (CCC) complexes facilitating endosomal trafficking of cell surface receptors. Hepatic COMMD1 inactivation decreases CCDC22 and CCDC93 protein levels, impairs the recycling of the low-density lipoprotein receptor (LDLR), and increases plasma LDL cholesterol levels in mice. However, whether any of the other COMMD members function similarly as COMMD1, and whether perturbation in the CCC complex promotes atherogenesis remain unclear...
March 15, 2018: Circulation Research
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