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N-glycosylation

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https://www.readbyqxmd.com/read/28104755/n-glycosylation-of-human-sphingomyelin-phosphodiesterase-acid-like-3a-smpdl3a-is-essential-for-stability-secretion-and-activity
#1
Mathew Traini, Raani Kumaran, Morten Thaysen-Andersen, Maaike Kockx, Wendy Jessup, Leonard Kritharides
Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a recently identified phosphodiesterase, which is a secreted N -linked glycoprotein. SMPDL3A is highly homologous to acid sphingomyelinase (aSMase), but unlike aSMase can not cleave sphingomyelin. Rather, SMPDL3A hydrolyzes nucleotide tri- and diphosphates and their derivatives. While recent structural studies have shed light on these unexpected substrate preferences, many other aspects of SMPDL3A biology which may give insight into its function in vivo remain obscure...
January 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28093152/re-n-glycosylation-critically-regulates-function-of-oxalate-transporter-slc26a6
#2
Dean G Assimos
No abstract text is available yet for this article.
February 2017: Journal of Urology
https://www.readbyqxmd.com/read/28092368/molecular-insights-into-lipid-assisted-ca-2-regulation-of-the-trp-channel-polycystin-2
#3
Martin Wilkes, M Gregor Madej, Lydia Kreuter, Daniel Rhinow, Veronika Heinz, Silvia De Sanctis, Sabine Ruppel, Rebecca M Richter, Friederike Joos, Marina Grieben, Ashley C W Pike, Juha T Huiskonen, Elisabeth P Carpenter, Werner Kühlbrandt, Ralph Witzgall, Christine Ziegler
Polycystin-2 (PC2), a calcium-activated cation TRP channel, is involved in diverse Ca(2+) signaling pathways. Malfunctioning Ca(2+) regulation in PC2 causes autosomal-dominant polycystic kidney disease. Here we report two cryo-EM structures of distinct channel states of full-length human PC2 in complex with lipids and cations. The structures reveal conformational differences in the selectivity filter and in the large exoplasmic domain (TOP domain), which displays differing N-glycosylation. The more open structure has one cation bound below the selectivity filter (single-ion mode, PC2SI), whereas multiple cations are bound along the translocation pathway in the second structure (multi-ion mode, PC2MI)...
January 16, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28089609/de-immunized-and-functional-therapeutic-deft-versions-of-a-long-lasting-recombinant-alpha-interferon-for-antiviral-therapy
#4
Eduardo F Mufarrege, Sofía Giorgetti, Marina Etcheverrigaray, Frances Terry, William Martin, Anne S De Groot
Interferon α (IFN-α) exerts potent antiviral, immunomodulatory, and antiproliferative activity and have proven clinical utility in chronic hepatitis B and C virus infections. However, repeated IFN-α administration induces neutralizing antibodies (NAb) against the therapeutic in a significant number of patients. Associations between IFN-α immunogenicity and loss of efficacy have been described. So as to improve the in vivo biological efficacy of IFN-α, a long lasting hyperglycosylated protein (4N-IFN) derived from IFN-α2b wild type (WT-IFN) was developed...
January 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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
#5
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/28087337/tunicamycin-impairs-olfactory-learning-and-synaptic-plasticity-in-the-olfactory-bulb
#6
Jia Tong, Fumino Okutani, Yoshihiro Murata, Mustuo Taniguchi, Toshiharu Namba, Yu-Jie Wang, Hideto Kaba
Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory...
January 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28077793/integrated-proteomic-and-n-glycoproteomic-analyses-of-doxorubicin-sensitive-and-resistant-ovarian-cancer-cells-reveal-glycoprotein-alteration-in-protein-abundance-and-glycosylation
#7
Yanlong Ji, Shasha Wei, Junjie Hou, Chengqian Zhang, Peng Xue, Jifeng Wang, Xiulan Chen, Xiaojing Guo, Fuquan Yang
Ovarian cancer is one of the most common cancer among women in the world, and chemotherapy remains the principal treatment for patients. However, drug resistance is a major obstacle to the effective treatment of ovarian cancers and the underlying mechanism is not clear. An increased understanding of the mechanisms that underline the pathogenesis of drug resistance is therefore needed to develop novel therapeutics and diagnostic. Herein, we report the comparative analysis of the doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI/ADR-RES cells using integrated global proteomics and N-glycoproteomics...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077298/the-underestimated-n-glycomes-of-lepidopteran-species
#8
Rhiannon Stanton, Alba Hykollari, Barbara Eckmair, Daniel Malzl, Martin Dragosits, Dieter Palmberger, Ping Wang, Iain B H Wilson, Katharina Paschinger
BACKGROUND: Insects are significant to the environment, agriculture, health and biotechnology. Many of these aspects display some relationship to glycosylation, e.g., in case of pathogen binding or production of humanised antibodies; for a long time, it has been considered that insect N-glycosylation potentials are rather similar and simple, but as more species are glycomically analysed in depth, it is becoming obvious that there is indeed a large structural diversity and interspecies variability...
January 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28074929/evolution-of-protein-n-glycosylation-process-in-golgi-apparatus-which-shapes-diversity-of-protein-n-glycan-structures-in-plants-animals-and-fungi
#9
Peng Wang, Hong Wang, Jiangtao Gai, Xiaoli Tian, Xiaoxiao Zhang, Yongzhi Lv, Yi Jian
Protein N-glycosylation (PNG) is crucial for protein folding and enzymatic activities, and has remarkable diversity among eukaryotic species. Little is known of how unique PNG mechanisms arose and evolved in eukaryotes. Here we demonstrate a picture of onset and evolution of PNG components in Golgi apparatus that shaped diversity of eukaryotic protein N-glycan structures, with an emphasis on roles that domain emergence and combination played on PNG evolution. 23 domains were identified from 24 known PNG genes, most of which could be classified into a single clan, indicating a single evolutionary source for the majority of the genes...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073834/dynamic-and-coordinated-single-molecular-interactions-at-tm4sf5-enriched-microdomains-guide-invasive-behaviors-in-2-and-3-dimensional-environments
#10
Hye-Jin Kim, Sojung Kwon, Seo Hee Nam, Jae Woo Jung, Minkyung Kang, Jihye Ryu, Ji Eon Kim, Jin-Gyu Cheong, Chang Yun Cho, Somi Kim, Dae-Geun Song, Yong-Nyun Kim, Tai Young Kim, Min-Kyo Jung, Kyung-Min Lee, Chan-Gi Pack, Jung Weon Lee
Membrane proteins sense extracellular cues and transduce intracellular signaling to coordinate directionality and speed during cellular migration. They are often localized to specific regions, as with lipid rafts or tetraspanin-enriched microdomains; however, the dynamic interactions of tetraspanins with diverse receptors within tetraspanin-enriched microdomains on cellular surfaces remain largely unexplored. Here, we investigated effects of tetraspan(in) TM4SF5 (transmembrane 4 L six family member 5)-enriched microdomains (T5ERMs) on the directionality of cell migration...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28069378/role-of-n-glycosylation-on-zika-virus-e-protein-secretion-viral-assembly-and-infectivity
#11
M Mossenta, S Marchese, M Poggianella, J L Slon Campos, O R Burrone
Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells...
January 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28067448/oled-loki-as-a-catalyst-for-tertiary-amine-and-hydroxamate-glycosylation
#12
Ryan R Hughes, Khaled A Shaaban, Jianjun Zhang, Hongnan Cao, George N Phillips, Jon S Thorson
We describe the ability of an engineered glycosyltransferase (OleD Loki) to catalyze the N-glycosylation of tertiary-amine-containing drugs and trichostatin hydroxamate glycosyl ester formation. As such, this study highlights the first bacterial model catalyst for tertiary-amine N-glycosylation and further expands the substrate scope and synthetic potential of engineered OleDs. In addition, this work could open the door to the discovery of similar capabilities among other permissive bacterial glycosyltransferases...
January 9, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28067406/ninjurin1-assembles-into-a-homomeric-protein-complex-maintained-by-n-linked-glycosylation
#13
Sung-Jin Bae, Min Wook Shin, Ran Hee Kim, Dongyoon Shin, Taekwon Son, Hee-Jun Wee, Kyu-Won Kim
Ninjurin1 (Ninj1) is a cell surface protein known as a homophilic adhesion molecule. Previous studies have shown a trans-interaction of Ninj1 between immune cells and endothelial cells; however, little is known about Ninj1 modification and structure in the cis-interaction. We showed that Ninj1 assembles into a homomeric complex via a cis-interaction mediated by the intracellular region and N-glycosylation at Asn(60) . We identified cis-interaction between Ninj1 proteins using CFP- and YFP-tagged Ninj1 by Förster resonance energy transfer using a confocal microscope and fluorescence-activated cell sorter...
January 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28060820/proteolytic-origin-of-the-soluble-human-il-6r-in-vivo-and-a-decisive-role-of-n-glycosylation
#14
Steffen Riethmueller, Prasath Somasundaram, Johanna C Ehlers, Chien-Wen Hung, Charlotte M Flynn, Juliane Lokau, Maria Agthe, Stefan Düsterhöft, Yijue Zhu, Joachim Grötzinger, Inken Lorenzen, Tomas Koudelka, Kosuke Yamamoto, Ute Pickhinke, Rielana Wichert, Christoph Becker-Pauly, Marisa Rädisch, Alexander Albrecht, Markus Hessefort, Dominik Stahnke, Carlo Unverzagt, Stefan Rose-John, Andreas Tholey, Christoph Garbers
Signaling of the cytokine interleukin-6 (IL-6) via its soluble IL-6 receptor (sIL-6R) is responsible for the proinflammatory properties of IL-6 and constitutes an attractive therapeutic target, but how the sIL-6R is generated in vivo remains largely unclear. Here, we use liquid chromatography-mass spectrometry to identify an sIL-6R form in human serum that originates from proteolytic cleavage, map its cleavage site between Pro-355 and Val-356, and determine the occupancy of all O- and N-glycosylation sites of the human sIL-6R...
January 2017: PLoS Biology
https://www.readbyqxmd.com/read/28059703/glycolysis-and-glutaminolysis-cooperatively-control-t-cell-function-by-limiting-metabolite-supply-to-n-glycosylation
#15
Lindsey Araujo, Phillip Khim, Haik Mkhikian, Christie-Lynn Mortales, Michael Demetriou
Rapidly proliferating cells switch from oxidative phosphorylation to aerobic glycolysis plus glutaminolysis, markedly increasing glucose and glutamine catabolism. Although Otto Warburg first described aerobic glycolysis in cancer cells >90 years ago, the primary purpose of this metabolic switch remains controversial. The hexosamine biosynthetic pathway requires glucose and glutamine for de novo synthesis of UDP-GlcNAc, a sugar-nucleotide that inhibits receptor endocytosis and signaling by promoting N-acetylglucosamine branching of Asn (N)-linked glycans...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28057501/cloning-and-characterization-of-pyruvate-carboxylase-gene-responsible-for-calcium-malate-overproduction-in-penicillium-viticola-152-and-its-expression-analysis
#16
Ibrar Khan, Sadia Qayyum, Shehzad Ahmed, Farhana Maqbool, Isfahan Tauseef, Kashif Syed Haleem, Zhen-Ming Chi
In this study, a pyruvate carboxylase gene (PYC) from a marine fungus Penicillium viticola 152 isolated from marine algae was cloned and characterized by using Genome Walking method. An open reading frame (ORF) of The PYC gene (accession number: KM593097) had 3582bp encoding 1193 amino acid protein (isoelectric point: 5.01) with a calculated molecular weight of 131.2757kDa. A putative promoter (intronless) of the gene was located at -666bp and contained a TATA box, several CAAT boxes, the 5'-SYGGRG-3' and a 5'-HGATAR-3' sequences...
January 2, 2017: Gene
https://www.readbyqxmd.com/read/28056108/molecular-characterization-of-n-glycan-degradation-and-transport-in-streptococcus-pneumoniae-and-its-contribution-to-virulence
#17
Melissa Robb, Joanne K Hobbs, Shireen A Woodiga, Sarah Shapiro-Ward, Michael D L Suits, Nicholas McGregor, Harry Brumer, Hasan Yesilkaya, Samantha J King, Alisdair B Boraston
The carbohydrate-rich coating of human tissues and cells provide a first point of contact for colonizing and invading bacteria. Commensurate with N-glycosylation being an abundant form of protein glycosylation that has critical functional roles in the host, some host-adapted bacteria possess the machinery to process N-linked glycans. The human pathogen Streptococcus pneumoniae depolymerizes complex N-glycans with enzymes that sequentially trim a complex N-glycan down to the Man3GlcNAc2 core prior to the release of the glycan from the protein by endo-β-N-acetylglucosaminidase (EndoD), which cleaves between the two GlcNAc residues...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28054967/expression-purification-and-biophysical-characterization-of-a-secreted-anthrax-decoy-fusion-protein-in-nicotiana-benthamiana
#18
Kalimuthu Karuppanan, Sifti Duhra-Gill, Muchena J Kailemia, My L Phu, Carlito B Lebrilla, Abhaya M Dandekar, Raymond L Rodriguez, Somen Nandi, Karen A McDonald
Anthrax toxin receptor-mediated drug development for blocking anthrax toxin action has received much attention in recent decades. In this study, we produced a secreted anthrax decoy fusion protein comprised of a portion of the human capillary morphogenesis gene-2 (CMG2) protein fused via a linker to the fragment crystallizable (Fc) domain of human immunoglobulin G1 in Nicotiana benthamiana plants using a transient expression system. Using the Cauliflower Mosaic Virus (CaMV) 35S promoter and co-expression with the p19 gene silencing suppressor, we were able to achieve a high level of recombinant CMG2-Fc-Apo (rCMG2-Fc-Apo) protein accumulation...
January 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28052259/conformational-freedom-of-the-lrp6-ectodomain-is-regulated-by-n-glycosylation-and-the-binding-of-the-wnt-antagonist-dkk1
#19
Kyoko Matoba, Emiko Mihara, Keiko Tamura-Kawakami, Naoyuki Miyazaki, Shintaro Maeda, Hidenori Hirai, Samuel Thompson, Kenji Iwasaki, Junichi Takagi
LDL-receptor-related protein 6 (LRP6) is a single-pass membrane glycoprotein with a large modular ectodomain and forms a higher order signaling platform upon binding Wnt ligands on the cell surface. Although multiple crystal structures are available for fragments of the LRP6 ectodomain, we lack a consensus view on the overall molecular architecture of the full-length LRP6 and its dynamic aspects. Here, we used negative-stain electron microscopy to probe conformational states of the entire ectodomain of LRP6 in solution and found that the four-module ectodomain undergoes a large bending motion hinged at the junction between the second and the third modules...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28049948/abnormal-n-glycosylation-of-a-novel-missense-creatine-transporter-mutant-g561r-associated-with-cerebral-creatine-deficiency-syndromes-alters-transporter-activity-and-localization
#20
Tatsuki Uemura, Shingo Ito, Yusuke Ohta, Masanori Tachikawa, Takahito Wada, Tetsuya Terasaki, Sumio Ohtsuki
Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). This results in low cerebral creatine levels, and patients exhibit mental retardation, poor language skills and epilepsy. We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation...
2017: Biological & Pharmaceutical Bulletin
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