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Post translational modification

Andrew J Fisher, Peter A Beal
All messenger RNAs in eukaryotes are modified co-transcriptionally and post-transcriptionally. They are all capped at the 5'-end and polyadenylated at the 3'-end. However, many mRNAs are also found to be chemically modified internally for regulation of mRNA processing, translation, stability, and to recode the message. This review will briefly summarize the structural basis for formation of the two most common modifications found at internal sites in mRNAs; methylation and deamination. The structures of the enzymes that catalyze these modifications show structural similarity to other family members within each modifying enzyme class...
June 15, 2018: Current Opinion in Structural Biology
Qi Tang, Peng Wu, Huiqing Chen, Guohui Li
Protein ubiquitination is a highly conserved post-translational modification affecting various biological processes including viral propagation. Ubiquitination has multiple effects on viral propagation, including viral genome uncoating, viral replication, and immune evasion. Ubiquitination of viral proteins is triggered by the ubiquitin-proteasome system (UPS). This involves the covalent attachment of the highly conserved 76 amino acid residue ubiquitin protein to target proteins by the consecutive actions of E1, E2 and E3 enzymes, and the 26S proteasome that together form a multiprotein complex that degrades target proteins...
June 15, 2018: Life Sciences
Xin Liu, Mingkun Yang, Yan Wang, Zhuo Chen, Jia Zhang, Xiaohuang Lin, Feng Ge, Jindong Zhao
Lysine succinylation is a newly-identified protein post-translational modification and plays important roles in various biological pathways in both prokaryotes and eukaryotes, but its extent and function in photosynthetic organisms remain largely unknown. Here, we performed the first systematic studies of lysine succinylation in cyanobacteria, which are the only prokaryotes capable of oxygenic photosynthesis and the established model organisms for studying photosynthetic mechanisms. By using mass spectrometry analysis in combination with the enrichment of succinylated peptides from digested cell lysates, we identified 1704 lysine succinylation sites on 691 proteins in a model cyanobacterium Synechococcus sp...
April 18, 2018: Plant & Cell Physiology
Mechthild Pohlschroder, Friedhelm Pfeiffer, Stefan Schulze, Mohd Farid Abdul Halim
Cell surfaces are critical for diverse functions across all domains of life, from cell-cell communication and nutrient uptake to cell stability and surface attachment. While certain aspects of the mechanisms supporting the biosynthesis of the archaeal cell surface are unique, likely due to important differences in cell surface compositions between domains, others are shared with bacteria or eukaryotes or both. Based on recent studies completed on a phylogenetically diverse array of archaea, from a wide variety of habitats, here we discuss advances in the characterization of mechanisms underpinning archaeal cell surface biogenesis...
June 15, 2018: FEMS Microbiology Reviews
Archana Shubhakar, Poh-Choo Pang, Daryl L Fernandes, Anne Dell, Daniel I R Spencer, Stuart M Haslam
Glycosylation is considered one of the most complex and structurally diverse post-translational modifications of proteins. Glycans play important roles in many biological processes such as protein folding, regulation of protein stability, solubility and serum half-life. One of the ways to study glycosylation is systematic structural characterizations of protein glycosylation utilizing glycomics methodology based around mass spectrometry (MS). The most prevalent bottleneck stages for glycomic analyses is laborious sample preparation steps...
June 16, 2018: Glycoconjugate Journal
Moin A Saleem
Soluble urokinase-type plasminogen activator -(suPAR) is an inflammatory signal with pleiotropic biological effects depending on context and post-translational modifications. Recently, [Hayek, et al: Nat Med 2017; 23: 945-953] it has been found that there is a link between suPAR and renal disease in several guises, and a key question is whether it is a driver or a marker of renal disease, and if so of which types of kidney damage. Subject of Review: Circulating suPAR has been postulated to cause acute proteinuric kidney disease, specifically focal segmental glomerulosclerosis (FSGS), though both the animal models and clinical data in the original reports have been challenged...
June 15, 2018: Nephron
Anna Sato, Jun-Dal Kim, Hayase Mizukami, Misaki Nakashima, Koichiro Kako, Junji Ishida, Atsuo Itakura, Satoru Takeda, Akiyoshi Fukamizu
INTRODUCTION: In mammals, the placenta is an organ that is required to maintain the development of fetus during pregnancy. Although the proper formation of placenta is in part regulated by the post-translational modifications of proteins, little is known regarding protein arginine methylation during placental development. Here, we characterized developmental expression of protein arginine methyltransferase 1 (PRMT1) in mouse placentas. METHODS: Expression levels of PRMT1 mRNA and protein in placentas were investigated using the real-time quantitative PCR and Western blot, respectively...
May 2018: Placenta
Shan-Ling Liu, Feng-Hou Gao
Small ubiquitin-like modifier (SUMOylation) is a reversible post-translational modification, which plays important roles in numerous biological processes. SUMO could be covalently attached to target proteins in an isopeptide bond manner that occurs via a lysine ε-amino group on the target proteins and the glycine on SUMO C-terminus. This covalent binding could affect the subcellular localization and stability of target proteins. SUMO modification can be reversed by members of the Sentrin/SUMO-specific proteases (SENPs) family, which are highly evolutionarily conserved from yeast to human...
June 13, 2018: Biochimie
Yasin Pourfarjam, Jessica Ventura, Igor Kurinov, Ahra Cho, Joel Moss, In-Kwon Kim
ADP-ribosyl-acceptor hydrolase 3 (ARH3) plays important roles in regulation of poly(ADP-ribosy)lation, a reversible post-translational modification, and in maintenance of genomic integrity. ARH3 degrades poly(ADP-ribose) to protect cells from poly(ADP-ribose)-dependent cell death, reverses serine-mono(ADP-ribosy)lation, and hydrolyzes O -acetyl-ADP-ribose, a product of Sirtuin-catalyzed histone deacetylation. ARH3 preferentially hydrolyzes O-linkages attached to the anomeric C1″ of ADP-ribose; however, how ARH3 specifically recognizes and cleaves structurally diverse substrates remains unknown...
June 15, 2018: Journal of Biological Chemistry
Jan Beckendorf, Maarten M G van den Hoogenhof, Johannes Backs
In the cardiomyocyte, CaMKII has been identified as a nodal influencer of excitation-contraction and also excitation-transcription coupling. Its activity can be regulated in response to changes in intracellular calcium content as well as after several post-translational modifications. Some of the effects mediated by CaMKII may be considered adaptive, while effects of sustained CaMKII activity may turn into the opposite and are detrimental to cardiac integrity and function. As such, CaMKII has long been noted as a promising target for pharmacological inhibition, but the ubiquitous nature of CaMKII has made it difficult to target CaMKII specifically where it is detrimental...
June 15, 2018: Basic Research in Cardiology
Lara K Abramowitz, John A Hanover
O-GlcNAcylation is an essential post-translational modification important for integrating metabolism with cell physiology. Using diverse model systems, studies of this evolutionarily conserved intracellular glycosylation have highlighted its role in stem cell maintenance, lineage specification and disease. Although discovered over 30 years ago, the study of O-GlcNAc continues to evolve and uncover surprising roles for O-GlcNAc and the enzymes of O-GlcNAc cycling: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA)...
June 14, 2018: FEBS Letters
Vincent Vanheule, Mieke Metzemaekers, Rik Janssens, Sofie Struyf, Paul Proost
Chemokines are important proteins involved in the regulation of directed leukocyte migration during inflammation and the homeostatic homing of immune cells. In addition, they play a role in angiogenesis, hematopoiesis, organogenesis, tumor growth and metastasis. Therefore, the chemokine/chemokine receptor network is highly complex and needs to be tightly controlled. An important mechanism of fine-tuning chemokine activity and reducing its apparent redundancy is post-translational modification (PTM) of chemokines and their receptors...
September 2018: Cytokine
Galit Alter, Tom H M Ottenhoff, Simone A Joosten
Antibodies are antigen recognizing immunoglobulins with an amazingly diverse repertoire in the antigen specific domain. The diversity of the antibody response is further increased by modifications such as somatic recombination and hypermutation. Furthermore, variation in the isotype and post-translational modifications such as Fc glycosylation further increase diversity of the effector functions. In particular variations in the glycan structures contribute significantly to the functional capacities of the antibodies...
June 11, 2018: Seminars in Immunology
Jingshu Zhang, Yun Lan, Ming Yuan Li, Mart Matthias Lamers, Maxime Fusade-Boyer, Elizabeth Klemm, Christoph Thiele, Joseph Ashour, Sumana Sanyal
Ubiquitylation is one of the most versatile protein post-translational modifications and is frequently altered during virus infections. Here we employed a functional proteomics screen to identify host proteins that are differentially ubiquitylated upon dengue virus (DENV) infection. Among the several differentially modified proteins identified in infected cells was AUP1, a lipid droplet-localized type-III membrane protein, which exists predominantly in the mono-ubiquitylated form. AUP1 associated with DENV NS4A and relocalized from lipid droplets to autophagosomes upon infection...
June 13, 2018: Cell Host & Microbe
Aditya Kiran Gatta, Raghu Chandrashekhar Hariharapura, Nayanabhirama Udupa, Meka Sreenivasa Reddy, Venkata Rao Josyula
RNA interference has become a tool of choice in the development of drugs in various therapeutic areas of Post Transcriptional Gene Silencing (PTGS). The critical element in developing successful RNAi therapeutics lies in designing small interfering RNA (siRNA) using an efficient algorithm satisfying the designing criteria. Further, translation of siRNA from bench-side to bedside needs an efficient delivery system and/or chemical modification. Areas covered: This review emphasizes the importance of dicer, the criteria for efficient siRNA design, the currently available algorithms and strategies to overcome off-target effects, immune stimulatory effects and endosomal trap...
June 14, 2018: Expert Opinion on Drug Discovery
Wanlin Jiang, Devendra K Agrawal, Chandra S Boosani
Histone modifications are the key epigenetic mechanisms that have been identified to regulate gene expression in many human diseases. However, in the early developmental stages, such as in utero and the postnatal stages, histone modifications are essential for gene regulation and cell growth. Atherosclerosis represents a classical example of the involvement of different cell types, and their cumulative effects in the development of atheroma and the progression of the disease. Post translational modifications on proteins either induces their functional activity or renders them inactive...
June 6, 2018: Molecular Medicine Reports
Dan Li, Lei Wang, Brandon F Maziuk, Xudong Yao, Benjamin Wolozin, Yong Ku Cho
Antibodies are essential biochemical reagents for detecting protein post-translational modifications (PTMs) in complex samples. However, recent efforts in developing PTM-targeting antibodies have reported frequent non-specific binding and limited affinity of such antibodies. To address these challenges, we investigated whether directed evolution could be applied to improve the affinity of a high-specificity antibody targeting phospho-threonine 231 (pT231) of the human microtubule-associated protein tau. On the basis of existing structural information, we hypothesized that improving antibody affinity may come at the cost of loss in specificity...
June 13, 2018: Journal of Biological Chemistry
Swastika Sanyal, Lucia Molnarova, Judita Richterova, Barbora Huraiova, Zsigmond Benko, Silvia Polakova, Ingrid Cipakova, Andrea Sevcovicova, Katarina Gaplovska-Kysela, Karl Mechtler, Lubos Cipak, Juraj Gregan
The canonical role of cohesin is to mediate sister chromatid cohesion. In addition, cohesin plays important roles in processes such as DNA repair and regulation of gene expression. Mounting evidence suggests that various post-translational modifications including phosphorylation, acetylation and SUMOylation regulate cohesin functions. Our mass-spectrometry analysis of cohesin purified from Schizosaccharomyces pombe cells revealed that the cohesin subunit Psm1 is methylated on two evolutionarily conserved lysine residues K536 and K1200...
June 13, 2018: Journal of Cell Science
Matthias Benoit, Lauriane Simon, Sophie Desset, Céline Duc, Sylviane Cotterell, Axel Poulet, Samuel Le Goff, Christophe Tatout, Aline V Probst
Developmental phase transitions are often characterized by changes in the chromatin landscape and heterochromatin reorganization. In Arabidopsis, clustering of repetitive heterochromatic loci into so-called chromocenters is an important determinant of chromosome organization in nuclear space. Here, we investigated the molecular mechanisms involved in chromocenter formation during the switch from a heterotrophic to a photosynthetically competent state during early seedling development. We characterized the spatial organization and chromatin features at centromeric and pericentromeric repeats and identified mutant contexts with impaired chromocenter formation...
June 13, 2018: New Phytologist
Maximilian Klingler, Clemens Decristoforo, Christine Rangger, Dominik Summer, Julie Foster, Jane K Sosabowski, Elisabeth von Guggenberg
Minigastrin (MG) analogs show high affinity to the cholecystokinin-2 receptor (CCK2R) and have therefore been intensively studied to find a suitable analog for imaging and treatment of CCK2R-expressing tumors. The clinical translation of the radioligands developed thus far has been hampered by high kidney uptake or low enzymatic stability. In this study, we aimed to develop new MG analogs with improved targeting properties stabilized against degradation through site-specific amino acid modifications. Method: Based on the lead structure of a truncated MG analog, four new MG derivatives with substitutions in the C -terminal part of the peptide (Trp-Met-Asp-Phe-NH2 ) were synthesized and derivatized with DOTA at the N -terminus for radiolabeling with trivalent radiometals...
2018: Theranostics
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