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post translation modification

L Renee Ruhaak, Gege Xu, Qiongyu Li, Elisha Goonatilleke, Carlito B Lebrilla
Glycomic and glycoproteomic analyses involve the characterization of oligosaccharides (glycans) conjugated to proteins. Glycans are produced through a complicated nontemplate driven process involving the competition of enzymes that extend the nascent chain. The large diversity of structures, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies of glycans all conspire to make the analysis arguably much more difficult than any other biopolymer. Furthermore, the large number of glycoforms associated with a specific protein site makes it more difficult to characterize than any post-translational modification...
March 19, 2018: Chemical Reviews
Sara Villa-Hernández, Rodrigo Bermejo
Proliferating cells need to accurately duplicate and pass their genetic material on to daughter cells. Problems during replication and partition challenge the structural and numerical integrity of chromosomes. Diverse mechanisms, as the DNA replication checkpoint, survey the correct progression of replication and couple it with other cell cycle events to preserve genome integrity. The structural maintenance of chromosomes (SMC) cohesin complex primarily contributes to chromosome duplication by mediating the tethering of newly replicated sister chromatids, thus assisting their equal segregation in mitosis...
March 16, 2018: Current Genetics
Alejandro Avilés-Reyes, Irlan Almeida Freires, Richard Besingi, Sangeetha Purushotham, Champion Deivanayagam, L Jeannine Brady, Jacqueline Abranches, José A Lemos
Protein glycosylation has been described as the most abundant and complex post-translational modification occurring in nature. Recent studies have enhanced our view of how this modification occurs in bacteria highlighting the role of protein glycosylation in various processes such as biofilm formation, virulence and host-microbe interactions. We recently showed that the collagen- and laminin-binding adhesin Cnm of the dental pathogen Streptococcus mutans is post-translationally modified by the PgfS glycosyltransferase...
March 16, 2018: Scientific Reports
Antoine Molaro, Janet M Young, Harmit S Malik
Eukaryotic genomes must accomplish both compact packaging for genome stability and inheritance, as well as accessibility for gene expression. They do so using post-translational modifications of four ancient canonical histone proteins (H2A, H2B, H3, and H4) and by deploying histone variants with specialized chromatin functions. Some histone variants are conserved across all eukaryotes, whereas others are lineage-specific. Here, we performed detailed phylogenomic analyses of "short H2A histone" variants found in mammalian genomes...
March 16, 2018: Genome Research
Andrew T Fenley, Ramu Anandakrishnan, Yared H Kidane, Alexey V Onufriev
BACKGROUND: Controlled modulation of nucleosomal DNA accessibility via post-translational modifications (PTM) is a critical component to many cellular functions. Charge-altering PTMs in the globular histone core-including acetylation, phosphorylation, crotonylation, propionylation, butyrylation, formylation, and citrullination-can alter the strong electrostatic interactions between the oppositely charged nucleosomal DNA and the histone proteins and thus modulate accessibility of the nucleosomal DNA, affecting processes that depend on access to the genetic information, such as transcription...
March 16, 2018: Epigenetics & Chromatin
Anne C Conibear, Markus Muttenthaler
The 7th Chemical Protein Synthesis Meeting took place in September 2017 in Haifa, Israel, bringing together 100 scientists from 11 countries. The cutting-edge scientific program included new synthetic strategies and ligation auxiliaries, novel insights into protein signaling and post-translational modifications, and a range of promising therapeutic applications.
March 15, 2018: Cell Chemical Biology
Shannon N Rhoads, Zachary T Monahan, Debra S Yee, Frank P Shewmaker
Subcellular mislocalization and aggregation of the human FUS protein occurs in neurons of patients with subtypes of amyotrophic lateral sclerosis and frontotemporal dementia. FUS is one of several RNA-binding proteins that can functionally self-associate into distinct liquid-phase droplet structures. It is postulated that aberrant interactions within the dense phase-separated state can potentiate FUS's transition into solid prion-like aggregates that cause disease. FUS is post-translationally modified at numerous positions, which affect both its localization and aggregation propensity...
March 16, 2018: International Journal of Molecular Sciences
S T Ayrton, X Chen, R M Bain, C J Pulliam, M Achmatowicz, T G Flick, D Ren, R G Cooks
Proof of concept evidence is presented for a new method for the determination of isoaspartate, an important post-translational modification. Chemical derivatization is performed using common reagents for the modification of carboxylic acids and shown to yield suitable diagnostic information with regard to isomerization at the aspartate residue. The diagnostic gas phase chemistry is probed by collision-induced dissociation mass spectrometry, on the timescale of the MS experiment and semi-quantitative calibration of the percentage of isoaspartate in a peptide sample is demonstrated...
March 15, 2018: Journal of the American Society for Mass Spectrometry
Nourdine Chakouri, Cyril Reboul, Doria Boulghobra, Adrien Kleindienst, Stéphane Nottin, Sandrine Gayrard, François Roubille, Stefan Matecki, Alain Lacampagne, Olivier Cazorla
BACKGROUND: The interplay between oxidative stress and other signaling pathways in the contractile machinery regulation during cardiac stress and its consequences on cardiac function remains poorly understood. We evaluated the effect of the crosstalk between β-adrenergic and redox signaling on post-translational modifications of sarcomeric regulatory proteins, Myosin Binding Protein-C (MyBP-C) and Troponin I (TnI). METHODS AND RESULTS: We mimicked in vitro high level of physiological cardiac stress by forcing rat hearts to produce high levels of oxidized glutathione...
May 1, 2018: International Journal of Cardiology
Chad J Miller, Benjamin E Turk
Protein phosphorylation is the most common reversible post-translational modification in eukaryotes. Humans have over 500 protein kinases, of which more than a dozen are established targets for anticancer drugs. All kinases share a structurally similar catalytic domain, yet each one is uniquely positioned within signaling networks controlling essentially all aspects of cell behavior. Kinases are distinguished from one another based on their modes of regulation and their substrate repertoires. Coupling specific inputs to the proper signaling outputs requires that kinases phosphorylate a limited number of sites to the exclusion of hundreds of thousands of off-target phosphorylation sites...
March 12, 2018: Trends in Biochemical Sciences
Yunan Zheng, Martin J Gilgenast, Sacha Hauc, Abhishek Chatterjee
Reversible post-translational modification (PTM) is a powerful and ubiquitous mechanism to regulate protein function. The mechanistic basis of the associated functional regulation by PTMs often involves the recruitment of interaction partners that selectively binds the modified protein. Identifying such functionally important protein-protein interactions that are uniquely triggered by PTMs remains difficult due to several technical challenges. To address this, here we develop technology to site-specifically incorporate two distinct noncanonical amino acids into recombinant proteins: one modeling a PTM of interest and the second harboring a photoaffinity probe...
March 15, 2018: ACS Chemical Biology
Céline Ronin, David Mendes Costa, Joana Tavares, Joana Faria, Fabrice Ciesielski, Paola Ciapetti, Terry K Smith, Jane MacDougall, Anabela Cordeiro-da-Silva, Iain K Pemberton
The de novo crystal structure of the Leishmania infantum Silent Information Regulator 2 related protein 1 (LiSir2rp1) has been solved at 1.99Å in complex with an acetyl-lysine peptide substrate. The structure is broadly commensurate with Hst2/SIRT2 proteins of yeast and human origin, reproducing many of the structural features common to these sirtuin deacetylases, including the characteristic small zinc-binding domain, and the larger Rossmann-fold domain involved in NAD+-binding interactions. The two domains are linked via a cofactor binding loop ordered in open conformation...
2018: PloS One
William R Critchley, Caroline Pellet-Many, Benjamin Ringham-Terry, Michael A Harrison, Ian C Zachary, Sreenivasan Ponnambalam
Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses. Different RTKs exhibit both basal and ligand-stimulated ubiquitination, linked to trafficking through different intracellular compartments including the secretory pathway, plasma membrane, endosomes and lysosomes...
March 15, 2018: Cells
James W Checco, Guo Zhang, Wangding Yuan, Ke Yu, Siyuan Yin, Rachel H Roberts-Galbraith, Peter M Yau, Elena V Romanova, Jian Jing, Jonathan V Sweedler
Neuropeptides in several animals undergo an unusual post-translational modification: the isomerization of an amino acid residue from the L-stereoisomer to the D-stereoisomer. The resulting D-amino acid-containing peptide (DAACP) often displays higher biological activity than its all-L-residue analogue, with the D-residue being critical for function in many cases. However, little is known about the full physiological roles played by DAACPs and few studies have examined the interaction of DAACPs with their cognate receptors...
March 15, 2018: ACS Chemical Biology
Jian Liu, Fuzhong Ouyang, Zhihao Zhao, Ruifang Gao, Rui Shi, Enhui Wu, Rui Lv, Guoqiang Xu
A dual maleimides (DuMal) tagging method has been developed for both relative and absolute quantitation of cysteine-containing peptides (CCPs) in combination with MALDI-TOF mass spectrometry. We choose a pair of maleimides with the minimal difference in their chemical structures, including N-Methylmaleimide (NMM) and N-Ethylmaleimide (NEM), which allow for tagging CCPs in the Michael Addition reaction with a high efficiency rapidly (~minutes). We have validated that the DuMal Tagging technique is sensitive and reliable in quantitative analysis of CCPs...
March 15, 2018: Chembiochem: a European Journal of Chemical Biology
Muthu K Shanmugam, Frank Arfuso, Surendar Arumugam, Arunachalam Chinnathambi, Bian Jinsong, Sudha Warrier, Ling Zhi Wang, Alan Prem Kumar, Kwang Seok Ahn, Gautam Sethi, Manikandan Lakshmanan
Oncogenesis is a multistep process mediated by a variety of factors including epigenetic modifications. Global epigenetic post-translational modifications have been detected in almost all cancers types. Epigenetic changes appear briefly and do not involve permanent changes to the primary DNA sequence. These epigenetic modifications occur in key oncogenes, tumor suppressor genes, and transcription factors, leading to cancer initiation and progression. The most commonly observed epigenetic changes include DNA methylation, histone lysine methylation and demethylation, histone lysine acetylation and deacetylation...
February 16, 2018: Oncotarget
Alexander Hogrebe, Louise von Stechow, Dorte B Bekker-Jensen, Brian T Weinert, Christian D Kelstrup, Jesper V Olsen
Comprehensive mass spectrometry (MS)-based proteomics is now feasible, but reproducible quantification remains challenging, especially for post-translational modifications such as phosphorylation. Here, we compare the most popular quantification techniques for global phosphoproteomics: label-free quantification (LFQ), stable isotope labeling by amino acids in cell culture (SILAC) and MS2 - and MS3 -measured tandem mass tags (TMT). In a mixed species comparison with fixed phosphopeptide ratios, we find LFQ and SILAC to be the most accurate techniques...
March 13, 2018: Nature Communications
Tadashige Nozaki, Yuka Sasaki, Itsuko Fukuda, Mayu Isumi, Keitaro Nakamoto, Takae Onodera, Mitsuko Masutani
Poly (ADP-ribose) polymerase family, member 1 (Parp1) has pleiotropic and disparate functions in multiple cellular signaling pathways through post-translational protein modification. It contributes to the regulation of various cellular processes, including DNA damage repair, cell death, and cell differentiation, genetically or epigenetically. Meanwhile, the functions of Parp1 in intercellular signaling remain to be established. To examine the functions of Parp1 in intercellular signaling, we examined microRNA (miRNA) regulation in exosomes derived from Parp1-deficient (Parp1-/- ) embryonic stem (ES) cells...
March 10, 2018: Biochemical and Biophysical Research Communications
Taku Kuwabara, Yukihide Matsui, Fumio Ishikawa, Motonari Kondo
The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4⁺ T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions...
March 12, 2018: International Journal of Molecular Sciences
Dongya Jia, Jun Hyoung Park, Kwang Hwa Jung, Herbert Levine, Benny Abraham Kaipparettu
Aerobic glycolysis, also referred to as the Warburg effect, has been regarded as the dominant metabolic phenotype in cancer cells for a long time. More recently, it has been shown that mitochondria in most tumors are not defective in their ability to carry out oxidative phosphorylation (OXPHOS). Instead, in highly aggressive cancer cells, mitochondrial energy pathways are reprogrammed to meet the challenges of high energy demand, better utilization of available fuels and macromolecular synthesis for rapid cell division and migration...
March 13, 2018: Cells
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