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Man Cao, Guodong Chen, Lina Wang, Pingping Wen, Shaoping Shi
The tyrosine residue has been identified as suffering three major post-translational modifications (PTMs) including nitration, sulfation, and phosphorylation, which could be involved in different physiological and pathological processes. Multiple tyrosine residues of the whole protein may be modified concurrently, where PTM of a single tyrosine may affect modification of other neighboring tyrosine residues. Hence, it is significant and beneficial to predict nitration, sulfation, and phosphorylation of tyrosine residues in the whole protein sequence...
May 18, 2018: Journal of Chemical Information and Modeling
Charlotte Gaviard, Isabelle Broutin, Pascal Cosette, Emmanuelle De, Thierry Jouenne, Julie Hardouin
Pseudomonas aeruginosa is a Multi-Drug Resistant human opportunistic pathogen largely involved in nosocomial infections. Unfortunately, effective antibacterial agents lacked. Explore its physiology at the post-translational modifications (PTMs) level may contribute to the renewal of combat tactics. Recently, lysine succinylation was discovered in bacteria and seems to be an interesting PTM. Here, we present the first succinylome and acetylome of P. aeruginosa PA14 cultured in the presence of 4 different carbon sources, using a two-dimensional immunoaffinity approach coupled with nano-liquid chromatograpy tandem mass spectrometry...
May 17, 2018: Journal of Proteome Research
Chan Gao, Xueyong Zhang, Chuanchao Zhang, Zhilei Sui, Meng Hou, Rucheng Dai, Zhongping Wang, Xianxu Zheng, Zengming Zhang
Herein, pressure-induced phase transitions of RDX up to 50 GPa were systematically studied under different compression conditions. Precise phase transition points were obtained based on high-quality Raman spectra with small pressure intervals. This favors the correctness of the theoretical formula for detonation and the design of a precision weapon. The experimental results indicated that α-RDX immediately transformed to γ-RDX at 3.5 GPa due to hydrostatic conditions and possible interaction between the penetrating helium and RDX, with helium gas as the pressure-transmitting medium (PTM)...
May 17, 2018: Physical Chemistry Chemical Physics: PCCP
Saima Umbreen, Jibril Lubega, Beimi Cui, Qiaona Pan, Jihong Jiang, Gary J Loake
Reactive nitrogen species (RNS) and their cognate redox signalling networks pervade almost all facets of plant growth, development, immunity and environmental interactions. The emerging evidence implies that specificity in redox signalling is achieved by a multi-layered molecular framework. This encompasses the production of redox cues in the locale of the given protein target and protein tertiary structures that convey the appropriate local chemical environment to support redox-based, post-translational modifications (PTMs)...
May 15, 2018: Journal of Experimental Botany
Jinyoung Park, Eun Joo Song
Aurora B is an important kinase involved in dynamic cellular events in mitosis. Aurora B activity is controlled by several post-translational modifications (PTMs). Among them, E3 ubiquitin ligase-mediated ubiquitination plays crucial roles in controlling the relocation and degradation of Aurora B. Aurora B, ubiquitinated by different E3 ligases, moves to the exact site for its mitotic function during metaphase-anaphase transition and is then degraded for cell cycle progression at the end of mitosis. However, how the stability of Aurora B is maintained until its degradation has been poorly understood...
May 16, 2018: BMB Reports
Xinyuan Zhao, Wanjun Zhang, Tong Liu, Hangyan Dong, Junjie Huang, Changqing Sun, Guangshun Wang, Xiaohong Qian, Weijie Qin
Liquid biopsies using body fluids have gained much attention in recent years due to their multiple advantages in clinical diagnosis, such as less/non-invasive collection, suitability for longitudinal disease monitoring, and better representation of tumor heterogeneity. As an attractive choice for liquid biopsy, urine proteins and their post-translational modifications (PTMs) have the potential to offer significant insights into physiological variations and pathological changes in the human body. However, due to the intrinsically large variability of urine proteins and their PTMs among different individuals, there is a high demand for strategies for high-throughput analysis of a large number of samples to obtain a comprehensive view and a reliable reference interval of the urine proteome...
August 1, 2018: Talanta
Takamitsu Hattori, Shohei Koide
Despite increasing demands for antibodies to post-translational modifications (PTMs), fundamental difficulties in molecular recognition of PTMs hinder the generation of highly functional anti-PTM antibodies using conventional methods. Recently, advanced approaches in protein engineering and design that have been established for biologics development were applied to successfully generating highly functional anti-PTM antibodies. Furthermore, structural analyses of anti-PTM antibodies revealed unprecedented binding modes that substantially increased the antigen-binding surface...
May 9, 2018: Current Opinion in Structural Biology
Arseniy Mikhail Belov, Li Zang, Roberto Sebastiano, Marcia R Santos, David R Bush, Barry L Karger, Alexander R Ivanov
High resolution capillary zone electrophoresis - mass spectrometry (CZE-MS) has been of increasing interest for the analysis of biopharmaceuticals. In this work, a combination of middle-down and intact CZE-MS analyses has been implemented for the characterization of a biotherapeutic monoclonal antibody (mAb) with a variety of post-translational modifications (PTMs) and glycosylation structures. Middle-down and intact CZE separations were performed in an acidified methanol-water background electrolyte on a capillary with a positively-charged coating (M7C4I) coupled to an Orbitrap mass spectrometer using a commercial sheathless interface (CESI)...
May 11, 2018: Electrophoresis
Simone Sidoli
Histones are the most abundant protein family in the cells of complex organisms such as mammals and, together with DNA, they define the backbone of chromatin. Histone PTMs are key players of chromatin biology, as they function as anchors for proteins that bind and modulate chromatin readout, including gene expression. Middle-down mass spectrometry (MS) has been optimized for about 10 years to study histone N-terminal tails, but it has been rarely applied to identify the role of co-existing histone marks in biology...
May 9, 2018: Proteomics
Yansong Miao, Teepiyanut Tipakornsaowapak, Liangzhen Zheng, Yuguang Mu, Eric Lewellyn
Actin filament assembly contributes to the endocytic pathway pleiotropically, with active roles in clathrin-dependent and clathrin-independent endocytosis as well as subsequent endosomal trafficking. Endocytosis comprises a series of dynamic events, including the initiation of membrane curvature, bud invagination, vesicle abscission, and subsequent vesicular transport. The ultimate success of endocytosis requires the coordinated activities of proteins that trigger actin polymerization, recruit actin-binding proteins (ABPs), and organize endocytic proteins (EPs) that promote membrane curvature through molecular crowding or scaffolding mechanisms...
May 2, 2018: FEBS Journal
Gabrielle Stetz, Amanda Tse, Gennady M Verkhivker
Post-translational modifications (PTMs) represent an important regulatory instrument that modulates structure, dynamics and function of proteins. The large number of PTM sites in the Hsp90 proteins that are scattered throughout different domains indicated that synchronization of multiple PTMs through a combinatorial code can be invoked as an important mechanism to orchestrate diverse chaperone functions and recognize multiple client proteins. In this study, we have combined structural and coevolutionary analysis with molecular simulations and perturbation response scanning analysis of the Hsp90 structures to characterize functional role of PTM sites in allosteric regulation...
May 2, 2018: Scientific Reports
Saar A M van der Laarse, Aneika C Leney, Albert J R Heck
A wide variety of protein post-translational modifications (PTMs) decorate cellular proteins, regulating their structure, interactions and ultimately their function. The density of co-occurring PTMs on proteins can be very high, where multiple PTMs can positively or negatively influence each others actions, nowadays termed PTM crosstalk. In this review we highlight recent progress in the area of PTM crosstalk, whereby we focus on crosstalk between protein phosphorylation and O-GlcNAcylation. These two PTMs largely target identical (i...
May 2, 2018: FEBS Journal
Shi-Rong Hong, Cuei-Ling Wang, Yao-Shen Huang, Yu-Chen Chang, Ya-Chu Chang, Ganesh V Pusapati, Chun-Yu Lin, Ning Hsu, Hsiao-Chi Cheng, Yueh-Chen Chiang, Wei-En Huang, Nathan C Shaner, Rajat Rohatgi, Takanari Inoue, Yu-Chun Lin
Tubulin post-translational modifications (PTMs) occur spatiotemporally throughout cells and are suggested to be involved in a wide range of cellular activities. However, the complexity and dynamic distribution of tubulin PTMs within cells have hindered the understanding of their physiological roles in specific subcellular compartments. Here, we develop a method to rapidly deplete tubulin glutamylation inside the primary cilia, a microtubule-based sensory organelle protruding on the cell surface, by targeting an engineered deglutamylase to the cilia in minutes...
April 30, 2018: Nature Communications
Daniel de Vega, Adrian C Newton, Ari Sadanandom
Microbes constantly challenge plants, and some can successfully infect their host and cause disease. Basal immunity against plant pathogens in many cases is not enough for survival and leads to disease and, ultimately, a premature death of the host plant. However, the plant immune system can be temporarily and even trans-generationally primed; this 'primed state' leads to changes in the plant involving transcriptional, post-translational, metabolic, physiological and epigenetic reprogramming, which enables fine-tuning defence mechanisms for a rapid and/or more robust response after abiotic and/or biotic stress...
April 30, 2018: FEBS Letters
Yaser Daanial Khan, Nouman Rasool, Waqar Hussain, Sher Afzal Khan, Kuo-Chen Chou
Among all the post-translational modifications (PTMs) of proteins, Phosphorylation is known to be the most important and highly occurring PTM in eukaryotes and prokaryotes. It has an important regulatory mechanism which is required in most of the pathological and physiological processes including neural activity and cell signalling transduction. The process of threonine phosphorylation modifies the threonine by the addition of a phosphoryl group to the polar side chain, and generates phosphothreonine sites...
April 25, 2018: Analytical Biochemistry
Marie-Soleil Gauthier, Zuhier Awan, Annie Bouchard, Josée Champagne, Sylvain Tessier, Denis Faubert, Katherine Chabot, Pierre Y Garneau, Rémi Rabasa-Lhoret, Nabil G Seidah, Paul M Ridker, Jacques Genest, Benoit Coulombe
BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that interacts with the low-density lipoprotein (LDL) receptor at the surface of hepatocytes to regulate circulating LDL cholesterol levels. High circulating PCSK9 levels have been associated with elevated LDL cholesterol. Recently, the Food and Drug Administration of the United States approved new LDL cholesterol-lowering drugs that specifically target the inhibition of PCSK9. Similar to most human proteins, PCSK9 exists in multiple forms as it is the target of posttranslational modifications (PTMs) such as proteolytic cleavage, phosphorylation, and others, which can affect its biological activity...
April 3, 2018: Journal of Clinical Lipidology
Jean Bigeard, Heribert Hirt
Mitogen-activated protein kinases (MAPKs) are conserved protein kinases in eukaryotes that establish signaling modules where MAPK kinase kinases (MAPKKKs) activate MAPK kinases (MAPKKs) which in turn activate MAPKs. In plants, they are involved in the signaling of multiple environmental stresses and developmental programs. MAPKs phosphorylate their substrates and this post-translational modification (PTM) contributes to the regulation of proteins. PTMs may indeed modify the activity, subcellular localization, stability or trans-interactions of modified proteins...
2018: Frontiers in Plant Science
Liang-Chin Huang, Karen E Ross, Timothy R Baffi, Harold Drabkin, Krzysztof J Kochut, Zheng Ruan, Peter D'Eustachio, Daniel McSkimming, Cecilia Arighi, Chuming Chen, Darren A Natale, Cynthia Smith, Pascale Gaudet, Alexandra C Newton, Cathy Wu, Natarajan Kannan
Many bioinformatics resources with unique perspectives on the protein landscape are currently available. However, generating new knowledge from these resources requires interoperable workflows that support cross-resource queries. In this study, we employ federated queries linking information from the Protein Kinase Ontology, iPTMnet, Protein Ontology, neXtProt, and the Mouse Genome Informatics to identify key knowledge gaps in the functional coverage of the human kinome and prioritize understudied kinases, cancer variants and post-translational modifications (PTMs) for functional studies...
April 25, 2018: Scientific Reports
Deepali Rathore, Anneliese Faustino, John Schiel, Eric Pang, Michael Boyne, Sarah Rogstad
Mass spectrometry (MS) is widely used in the characterization of biomolecules including peptide and protein therapeutics. These biotechnology products have seen rapid growth over the past few decades and continue to dominate the global pharmaceutical market. Advances in MS instrumentation and techniques have enhanced protein characterization capabilities and supported an increased development of biopharmaceutical products. Areas covered: This review describes recent developments in MS-based biotherapeutic analysis including sequence determination, post-translational modifications (PTMs) and higher order structure (HOS) analysis along with improvements in ionization and dissociation methods...
April 25, 2018: Expert Review of Proteomics
Mahmood Haj-Yahya, Hilal A Lashuel
The microtubule-associated protein Tau plays a central role in neurodegeneration and is a leading therapeutic target for the treatment of Alzheimer's disease (AD). Several lines of evidence suggest that post-translational modifications (PTMs) regulate the function(s) of Tau, including its subcellular localization, clearance, aggregation, toxicity, and pathology spreading. However, the lack of tools and methodologies that allow site-specific introduction of PTMs in Tau have limited our ability to dissect the role of PTMs in regulating Tau functions in health and disease...
April 23, 2018: Journal of the American Chemical Society
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