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membrane protein folding

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https://www.readbyqxmd.com/read/28330872/nadph-oxidase-1-supports-proliferation-of-colon-cancer-cells-by-modulating-reactive-oxygen-species-dependent-signal-transduction
#1
Agnes Juhasz, Susan Markel, Shikha Gaur, Han Liu, Jiamo Lu, Guojian Jiang, Xiwei Wu, Smitha Antony, Yongzhong Wu, Giovanni Melillo, Jennifer L Meitzler, Diana C Haines, Donna Butcher, Krishnendu Roy, James H Doroshow
Reactive oxygen species (ROS) play a critical role in cell signaling and proliferation. NADPH oxidase 1 (NOX1), a membrane-bound flavin dehydrogenase that generates superoxide, is highly expressed in colon cancer. To investigate the role that NOX1 plays in colon cancer growth, we used shRNA to decrease NOX1 expression stably in HT-29 human colon cancer cells. The 80-90% decrease in NOX1 expression achieved by RNAi produced a significant decline in ROS production and a G1/S block that translated into a 2-3-fold increase in tumor cell doubling time without increased apoptosis...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28330496/calcium-dysregulation-functional-calpainopathy-and-endoplasmic-reticulum-stress-in-sporadic-inclusion-body-myositis
#2
David R Amici, Iago Pinal-Fernandez, Davi A G Mázala, Thomas E Lloyd, Andrea M Corse, Lisa Christopher-Stine, Andrew L Mammen, Eva R Chin
Sporadic inclusion body myositis (IBM) is the most common primary myopathy in the elderly, but its pathoetiology is still unclear. Perturbed myocellular calcium (Ca(2+)) homeostasis can exacerbate many of the factors proposed to mediate muscle degeneration in IBM, such as mitochondrial dysfunction, protein aggregation, and endoplasmic reticulum stress. Ca(2+) dysregulation may plausibly be initiated in IBM by immune-mediated membrane damage and/or abnormally accumulating proteins, but no studies to date have investigated Ca(2+) regulation in IBM patients...
March 22, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28329302/sensitization-of-gram-negative-bacilli-to-host-antibacterial-proteins
#3
Joanna Jammal, Fadia Zaknoon, Galoz Kaneti, Ayelet S Hershkovits, Amram Mor
Towards addressing the need for novel alternatives to antibiotics, we attempted to sensitize Gram-negative bacilli (GNB) to innate antibacterial protagonists. We report a lipopeptide-like sequence (C10OOc12O) that inflicted outer-membrane damages at low micromolar range, whereas measurable bacterial growth inhibition in broth medium required >10-fold higher concentrations. In serum however, C10OOc12O induced antibacterial activity in a manner suppressible by anti-complements antibodies or heat treatment, and acted synergistically with exogenous lysozyme in broth and serum media...
March 4, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28325716/coproporphyrin-i-a-fluorescent-endogenous-optimal-probe-substrate-for-abcc2-mrp2-that-is-suitable-for-vesicle-based-mrp2-inhibition-assay
#4
Ravindranath Reddy Gilibili, Sagnik Chatterjee, Pravin Bagul, Kthleen W Mosure, Bokka Venkata Murali, T Thanga Mariappan, Sandhya Mandlekar, Yurong Lai
Inside-out-oriented membrane vesicles are useful tools to investigate whether a compound can be an inhibitor of efflux transporters such as multidrug-resistance associated protein 2 (MRP2). However, because of technical limitations of substrate diffusion and low dynamic uptake windows for interacting drugs used in clinic, estradiol-17β-glucuronide (E17βG) remains the probe substrate frequently used in MRP2 inhibition assays. Here we re-capitulated the sigmoidal kinetics of MRP2 mediated uptake of E17βG, with apparent Km and Vmax values 170 ±17 μM and 1447 ± 137 pmol/mg protein/min, respectively...
March 21, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28320964/in-vivo-optophysiology-reveals-that-g-protein-activation-triggers-osmotic-swelling-and-increased-light-scattering-of-rod-photoreceptors
#5
Pengfei Zhang, Robert J Zawadzki, Mayank Goswami, Phuong T Nguyen, Vladimir Yarov-Yarovoy, Marie E Burns, Edward N Pugh
The light responses of rod and cone photoreceptors have been studied electrophysiologically for decades, largely with ex vivo approaches that disrupt the photoreceptors' subretinal microenvironment. Here we report the use of optical coherence tomography (OCT) to measure light-driven signals of rod photoreceptors in vivo. Visible light stimulation over a 200-fold intensity range caused correlated rod outer segment (OS) elongation and increased light scattering in wild-type mice, but not in mice lacking the rod G-protein alpha subunit, transducin (Gαt), revealing these responses to be triggered by phototransduction...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320857/regulation-of-very-long-acyl-chain-ceramide-synthesis-by-acyl-coa-binding-protein
#6
Natalia Santos Ferreira, Hanne Engelsby, Ditte Neess, Samuel L Kelly, Giora Volpert, Alfred H Merrill, Anthony H Futerman, Nils J Faergeman
Ceramide and more complex sphingolipids constitute a diverse group of lipids, which serve important roles as structural entities of biological membranes and as regulators of cellular growth, differentiation, and development. Thus, ceramides are vital players in numerous diseases including metabolic and cardiovascular diseases as well as neurological disorders. Here we show that acyl coenzyme A binding protein (ACBP) potently facilitates very-long acyl chain ceramide synthesis. ACBP increases the activity of ceramide synthase 2 (CerS2) by more than 2-fold and CerS3 activity by 7-fold...
March 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28319895/impact-of-high-cholesterol-and-endoplasmic-reticulum-stress-on-metabolic-diseases-an-updated-mini-review
#7
REVIEW
Erdi Sozen, Nesrin Kartal Ozer
Endoplasmic reticulum (ER) is the major site of protein folding and calcium storage. Beside the role of ER in protein homeostasis, it controls the cholesterol production and lipid-membrane biosynthesis as well as surviving and cell death signaling mechanisms in the cell. It is well-documented that elevated plasma cholesterol induces adverse effects in cardiovascular diseases (CVDs), liver disorders, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatosis hepatitis (NASH), and metabolic diseases which are associated with oxidative and ER stress...
March 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#8
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319196/h-channels-in-embryonic-biomphalaria-glabrata-cell-membranes-putative-roles-in-snail-host-schistosome-interactions
#9
Brandon J Wright, Utibe Bickham-Wright, Timothy P Yoshino, Meyer B Jackson
The human blood fluke Schistosoma mansoni causes intestinal schistosomiasis, a widespread neglected tropical disease. Infection of freshwater snails Biomphalaria spp. is an essential step in the transmission of S. mansoni to humans, although the physiological interactions between the parasite and its obligate snail host that determine success or failure are still poorly understood. In the present study, the B. glabrata embryonic (Bge) cell line, a widely used in vitro model for hemocyte-like activity, was used to investigate membrane properties, and assess the impact of larval transformation proteins (LTP) on identified ion channels...
March 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28317993/capturing-the-multiscale-dynamics-of-membrane-protein-complexes-with-all-atom-mixed-resolution-and-coarse-grained-models
#10
Chenyi Liao, Xiaochuan Zhao, Jiyuan Liu, Severin T Schneebeli, John C Shelley, Jianing Li
The structures and dynamics of protein complexes are often challenging to model in heterogeneous environments such as biological membranes. Herein, we meet this fundamental challenge at attainable cost with all-atom, mixed-resolution, and coarse-grained models of vital membrane proteins. We systematically simulated five complex models formed by two distinct G protein-coupled receptors (GPCRs) in the lipid-bilayer membrane on the ns-to-μs timescales. These models, which suggest the swinging motion of an intracellular loop, for the first time, provide the molecular details for the regulatory role of such a loop...
March 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28315715/sab-mediates-mitochondrial-dysfunction-involved-in-imatinib-mesylate-induced-cardiotoxicity
#11
Tara P Chambers, Luis Santiesteban, David Gomez, Jeremy W Chambers
Imatinib mesylate is an effective treatment for chronic myelogenous leukemia and gastrointestinal stromal tumors. Although imatinib mesylate is highly tolerable, it has been implicated in severe congestive heart failure in mouse models and patients. A hallmark of imatinib mesylate-induced cardiotoxicity is mitochondrial dysfunction. The mitochondrial scaffold Sab has been implicated in facilitating signaling responsible for mitochondrial dysfunction in a c-Jun N-terminal Kinase (JNK)-dependent manner. We examined the impact of Sab-mediated signaling on imatinib mesylate cardiotoxicity in H9c2 rat cardiomyocyte-like cells...
March 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28315353/crystal-structure-of-the-extracellular-domain-of-the-human-dendritic-cell-surface-marker-cd83
#12
Christiane S Heilingloh, Stefan Klingl, Claudia Egerer-Sieber, Benedikt Schmid, Sigrid Weiler, Petra Mühl-Zürbes, Jörg Hofmann, Joachim D Stump, Heinrich Sticht, Mirko Kummer, Alexander Steinkasserer, Yves A Muller
CD83 is a type-I membrane protein and an efficient marker for identifying mature dendritic cells. Whereas membrane-bound full-length CD83 co-stimulates the immune system, a soluble variant (sCD83), consisting of the extracellular domain, only, displays strong immune-suppressive activities. Besides a prediction that sCD83 adopts a V-set Ig-like fold, however, little is known about the molecular architecture of CD83 and the mechanism by which CD83 exerts is function on dendritic cells and additional immune cells...
March 14, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28314230/toxicity-of-diatom-polyunsaturated-aldehydes-to-marine-bacterial-isolates-reveals-their-mode-of-action
#13
Milva Pepi, Hermann J Heipieper, Cecilia Balestra, Marco Borra, Elio Biffali, Raffaella Casotti
Diatoms produce and release polyunsaturated aldehydes (PUAs) during senescence in culture and at the end of blooms in nature and these compounds play different ecological roles, as infochemicals, allelochemicals and pheromones In order to elucidate the toxic effects of PUAs, we isolated six bacterial strains from the Mediterranean Sea during a diatom bloom and tested their tolerance to PUA in terms of growth and cell membrane properties. Based upon 16S rRNA sequencing, these bacteria were assigned to the genera Pseudomonas, Sufflavibacter, Halomonas, Vibrio, Idiomarina, and Labrenzia...
March 9, 2017: Chemosphere
https://www.readbyqxmd.com/read/28302718/a-unique-choanoflagellate-enzyme-rhodopsin-with-cyclic-nucleotide-phosphodiesterase-activity
#14
Kazuho Yoshida, Satoshi P Tsunoda, Leonid S Brown, Hideki Kandori
Photoactivated adenylyl cyclase (PAC) and guanylyl cyclase rhodopsin (Rh-GC) increase the concentrations of intracellular cyclic nucleotides upon illumination, serving as promising second-generation tools in optogenetics. To broaden arsenal of such tools, it is desirable to have light-activatable enzymes which can decrease cyclic nucleotide concentrations in cells. Here, we report on an unusual microbial rhodopsin which may be able to meet the demand. It is found in the choanoflagellate Salpingoeca rosetta and contains a C-terminal cyclic nucleotide phosphodiesterase (PDE) domain...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302513/expression-purification-and-enzymatic-characterization-of-undecaprenyl-pyrophosphate-phosphatase-from-vibrio-vulnificus
#15
Hsin-Yang Chang, Chia-Cheng Chou, Mao-Lun Wu, Andrew H J Wang
Undecaprenyl pyrophosphate phosphatase (UppP), a cell membrane integral enzyme, catalyzes the dephosphorylation of undecaprenyl pyrophosphate to undecaprenyl phosphate, which is an essential carrier lipid in bacterial cell wall synthesis. We previously purified E. coli UppP and concluded that its catalytic site is likely located in the periplasm. To search for additional natural UppP homologs to elucidate what constitutes a common catalytic mechanism and to gain a better chance of obtaining high-resolution crystal structural information, we expressed and purified recombinant Vibrio vulnificus UppP using E...
March 14, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28301138/a-secretion-amplification-role-for-salmonella-enterica-translocon-protein-sipd
#16
Anum Azam Glasgow, Han Teng Wong, Danielle Tullman-Ercek
The bacterial type III secretion system (T3SS) is an important target for enabling high-titer production of proteins of biotechnological interest as well as for synthetic biology applications that rely on protein delivery to host cells. The T3SS forms a membrane-embedded needle complex that is capped by the translocon proteins and extends into the extracellular space. The needle tip complex in Salmonella enterica consists of three translocon proteins: SipB, SipC, and SipD. It is known that knocking out sipD disrupts T3SS regulation to cause constitutive secretion of native proteins...
March 16, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28300160/comparison-of-proteomic-profiles-in-the-zebrafish-retina-during-experimental-degeneration-and-regeneration
#17
Karen Eastlake, Wendy E Heywood, Dhani Tracey-White, Erika Aquino, Emily Bliss, Gerardo R Vasta, Kevin Mills, Peng T Khaw, Mariya Moosajee, G Astrid Limb
Zebrafish spontaneously regenerate the retina after injury. Although the gene expression profile has been extensively studied in this species during regeneration, this does not reflect protein function. To further understand the regenerative process in the zebrafish, we compared the proteomic profile of the retina during injury and upon regeneration. Using two-dimensional difference gel electrophoresis (2D-DIGE) and label-free quantitative proteomics (quadrupole time of flight LC-MS/MS), we analysed the retina of adult longfin wildtype zebrafish at 0, 3 and 18 days after Ouabain injection...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28297675/unconventional-targeting-of-a-thiol-peroxidase-to-the-mitochondrial-intermembrane-space-facilitates-oxidative-protein-folding
#18
Paraskevi Kritsiligkou, Afroditi Chatzi, Georgia Charalampous, Aleksandr Mironov, Chris M Grant, Kostas Tokatlidis
Thiol peroxidases are conserved hydrogen peroxide scavenging and signaling molecules that contain redox-active cysteine residues. We show here that Gpx3, the major H2O2 sensor in yeast, is present in the mitochondrial intermembrane space (IMS), where it serves a compartment-specific role in oxidative metabolism. The IMS-localized Gpx3 contains an 18-amino acid N-terminally extended form encoded from a non-AUG codon. This acts as a mitochondrial targeting signal in a pathway independent of the hitherto known IMS-import pathways...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28295644/effect-of-vitrification-on-the-mrna-transcriptome-of-bovine-oocytes
#19
N Wang, C-Y Li, H-B Zhu, H-S Hao, H-Y Wang, C-L Yan, S-J Zhao, W-H Du, D Wang, Y Liu, Y-W Pang, X-M Zhao
Vitrification has been shown to decrease the developmental capacity of mammalian oocytes, and this is closely associated with the abnormal mRNA expressions of vitrified oocytes. However, the effect of vitrification on transcriptional machinery of oocytes examined by RNA sequencing (RNA-seq) has yet to be defined. In the present study, the mRNA transcriptomes of fresh and vitrified bovine oocytes were analysed by Smart-seq2 with the differently expressed genes determined by DEseq2 (an adjusted p-value of .05 and a minimum fold change of 2)...
March 12, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28295026/neuronal-entry-and-high-neurotoxicity-of-botulinum-neurotoxin-a-require-its-n-terminal-binding-sub-domain
#20
Jiafu Wang, Jianghui Meng, Marc Nugent, Minhong Tang, J Oliver Dolly
Botulinum neurotoxins (BoNTs) are the most toxic proteins known, due to inhibiting the neuronal release of acetylcholine and causing flaccid paralysis. Most BoNT serotypes target neurons by binding to synaptic vesicle proteins and gangliosides via a C-terminal binding sub-domain (HCC). However, the role of their conserved N-terminal sub-domain (HCN) has not been established. Herein, we created a mutant form of recombinant BoNT/A lacking HCN (rAΔHCN) and showed that the lethality of this mutant is reduced 3...
March 15, 2017: Scientific Reports
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