scholarly journals Post-translational Lysine Ac(et)ylation in Bacteria: A Biochemical, Structural, and Synthetic Biological Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Michael Lammers
Keyword(s):  
Protein Function ◽  
High Energy ◽  
Research Field ◽  
Dimensional Structure ◽  
Special Focus ◽  
Side Chains ◽  
Amino Group ◽  
Acetyl Phosphate ◽  
Post Translational Modification ◽  
Metabolic State

Ac(et)ylation is a post-translational modification present in all domains of life. First identified in mammals in histones to regulate RNA synthesis, today it is known that is regulates fundamental cellular processes also in bacteria: transcription, translation, metabolism, cell motility. Ac(et)ylation can occur at the ε-amino group of lysine side chains or at the α-amino group of a protein. Furthermore small molecules such as polyamines and antibiotics can be acetylated and deacetylated enzymatically at amino groups. While much research focused on N-(ε)-ac(et)ylation of lysine side chains, much less is known about the occurrence, the regulation and the physiological roles on N-(α)-ac(et)ylation of protein amino termini in bacteria. Lysine ac(et)ylation was shown to affect protein function by various mechanisms ranging from quenching of the positive charge, increasing the lysine side chains’ size affecting the protein surface complementarity, increasing the hydrophobicity and by interfering with other post-translational modifications. While N-(ε)-lysine ac(et)ylation was shown to be reversible, dynamically regulated by lysine acetyltransferases and lysine deacetylases, for N-(α)-ac(et)ylation only N-terminal acetyltransferases were identified and so far no deacetylases were discovered neither in bacteria nor in mammals. To this end, N-terminal ac(et)ylation is regarded as being irreversible. Besides enzymatic ac(et)ylation, recent data showed that ac(et)ylation of lysine side chains and of the proteins N-termini can also occur non-enzymatically by the high-energy molecules acetyl-coenzyme A and acetyl-phosphate. Acetyl-phosphate is supposed to be the key molecule that drives non-enzymatic ac(et)ylation in bacteria. Non-enzymatic ac(et)ylation can occur site-specifically with both, the protein primary sequence and the three dimensional structure affecting its efficiency. Ac(et)ylation is tightly controlled by the cellular metabolic state as acetyltransferases use ac(et)yl-CoA as donor molecule for the ac(et)ylation and sirtuin deacetylases use NAD+ as co-substrate for the deac(et)ylation. Moreover, the accumulation of ac(et)yl-CoA and acetyl-phosphate is dependent on the cellular metabolic state. This constitutes a feedback control mechanism as activities of many metabolic enzymes were shown to be regulated by lysine ac(et)ylation. Our knowledge on lysine ac(et)ylation significantly increased in the last decade predominantly due to the huge methodological advances that were made in fields such as mass-spectrometry, structural biology and synthetic biology. This also includes the identification of additional acylations occurring on lysine side chains with supposedly different regulatory potential. This review highlights recent advances in the research field. Our knowledge on enzymatic regulation of lysine ac(et)ylation will be summarized with a special focus on structural and mechanistic characterization of the enzymes, the mechanisms underlying non-enzymatic/chemical ac(et)ylation are explained, recent technological progress in the field are presented and selected examples highlighting the important physiological roles of lysine ac(et)ylation are summarized.

Protein acetylation as a means to regulate protein function in tune with metabolic state

2014 ◽  
Vol 42 (4) ◽  
pp. 1037-1042 ◽  
Author(s):  
Lei Shi ◽  
Benjamin P. Tu
Keyword(s):  
Energy Metabolism ◽  
Present Article ◽  
Protein Function ◽  
Protein Acetylation ◽  
Post Translational Modification ◽  
Metabolic State ◽  
Acetyl Coa ◽  
Acetyl Group ◽  
Regulate Protein

Protein acetylation has emerged as a prominent post-translational modification that can occur on a wide variety of proteins. The metabolite acetyl-CoA is a key intermediate in energy metabolism that also serves as the acetyl group donor in protein acetylation modifications. Therefore such acetylation modifications might be coupled to the intracellular availability of acetyl-CoA. In the present article, we summarize recent evidence suggesting that the particular protein acetylation modifications enable the regulation of protein function in tune with acetyl-CoA availability and thus the metabolic state of the cell.

scholarly journals Post-translational lysine ac(et)ylation in health, ageing and disease

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Anna-Theresa Blasl ◽  
Sabrina Schulze ◽  
Chuan Qin ◽  
Leonie G. Graf ◽  
Robert Vogt ◽  
...  
Keyword(s):  
Protein Function ◽  
Molecular Mechanisms ◽  
Research Field ◽  
Ageing Process ◽  
Post Translational Modification ◽  
Direct Role ◽  
Translational Machinery ◽  
Beneficial Effects ◽  
Cellular Processes ◽  
Technological Advances

Abstract The acetylation/acylation (ac(et)ylation) of lysine side chains is a dynamic post-translational modification (PTM) regulating fundamental cellular processes with implications on the organisms’ ageing process: metabolism, transcription, translation, cell proliferation, regulation of the cytoskeleton and DNA damage repair. First identified to occur on histones, later studies revealed the presence of lysine ac(et)ylation in organisms of all kingdoms of life, in proteins covering all essential cellular processes. A remarkable finding showed that the NAD+-dependent sirtuin deacetylase Sir2 has an impact on replicative lifespan in Saccharomyces cerevisiae suggesting that lysine acetylation has a direct role in the ageing process. Later studies identified sirtuins as mediators for beneficial effects of caloric/dietary restriction on the organisms’ health- or lifespan. However, the molecular mechanisms underlying these effects are only incompletely understood. Progress in mass-spectrometry, structural biology, synthetic and semi-synthetic biology deepened our understanding of this PTM. This review summarizes recent developments in the research field. It shows how lysine ac(et)ylation regulates protein function, how it is regulated enzymatically and non-enzymatically, how a dysfunction in this post-translational machinery contributes to disease development. A focus is set on sirtuins and lysine acyltransferases as these are direct sensors and mediators of the cellular metabolic state. Finally, this review highlights technological advances to study lysine ac(et)ylation.

scholarly journals Growth Promotion or Osmotic Stress Response: How SNF1-Related Protein Kinase 2 (SnRK2) Kinases Are Activated and Manage Intracellular Signaling in Plants

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1443
Author(s):  
Yoshiaki Kamiyama ◽  
Sotaro Katagiri ◽  
Taishi Umezawa
Keyword(s):  
Protein Kinase ◽  
Plant Growth ◽  
Osmotic Stress ◽  
Protein Function ◽  
Intracellular Signaling ◽  
Growth Promotion ◽  
Research Field ◽  
Dependent Manner ◽  
Related Protein ◽  
Wide Range

Reversible phosphorylation is a major mechanism for regulating protein function and controls a wide range of cellular functions including responses to external stimuli. The plant-specific SNF1-related protein kinase 2s (SnRK2s) function as central regulators of plant growth and development, as well as tolerance to multiple abiotic stresses. Although the activity of SnRK2s is tightly regulated in a phytohormone abscisic acid (ABA)-dependent manner, recent investigations have revealed that SnRK2s can be activated by group B Raf-like protein kinases independently of ABA. Furthermore, evidence is accumulating that SnRK2s modulate plant growth through regulation of target of rapamycin (TOR) signaling. Here, we summarize recent advances in knowledge of how SnRK2s mediate plant growth and osmotic stress signaling and discuss future challenges in this research field.

scholarly journals Post translational modifications of milk proteins in geographically diverse goat breeds

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
P. K. Rout ◽  
M. Verma
Keyword(s):  
Protein Function ◽  
Whey Proteins ◽  
Milk Proteins ◽  
Goat Milk ◽  
Peptide Sequence ◽  
Cow Milk ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Functional Roles ◽  
Dpp Iv

AbstractGoat milk is a source of nutrition in difficult areas and has lesser allerginicity than cow milk. It is leading in the area for nutraceutical formulation and drug development using goat mammary gland as a bioreactor. Post translational modifications of a protein regulate protein function, biological activity, stabilization and interactions. The protein variants of goat milk from 10 breeds were studied for the post translational modifications by combining highly sensitive 2DE and Q-Exactive LC-MS/MS. Here we observed high levels of post translational modifications in 201 peptides of 120 goat milk proteins. The phosphosites observed for CSN2, CSN1S1, CSN1S2, CSN3 were 11P, 13P, 17P and 6P, respectively in 105 casein phosphopeptides. Whey proteins BLG and LALBA showed 19 and 4 phosphosites respectively. Post translational modification was observed in 45 low abundant non-casein milk proteins mainly associated with signal transduction, immune system, developmental biology and metabolism pathways. Pasp is reported for the first time in 47 sites. The rare conserved peptide sequence of (SSSEE) was observed in αS1 and αS2 casein. The functional roles of identified phosphopeptides included anti-microbial, DPP-IV inhibitory, anti-inflammatory and ACE inhibitory. This is first report from tropics, investigating post translational modifications in casein and non-casein goat milk proteins and studies their interactions.

scholarly journals Editorial from the Editor in Chief: Impact factors and open access publishing

2006 ◽  
Vol 24 (4) ◽  
pp. 467-468
Author(s):  
Dieter H.H. Hoffmann
Keyword(s):  
Impact Factor ◽  
Ultrashort Pulses ◽  
Dense Matter ◽  
High Energy ◽  
Research Field ◽  
High Energy Density ◽  
Open Access Publishing ◽  
Impact Factors ◽  
Particle Beams ◽  
The Impact

The primary goal of Laser and Particle Beams as part of the Cambridge University Press is the dissemination of knowledge in our research field. How effective we are in this respect is not easy to determine. But the impact factor published annually in June by Thomson ISI® 2005 Journal Citation Reports (JCR), gives at least an indication and a method to compare other journals in the field. In this respect, Laser and Particle Beams is a journal with a very high ranking in the field of applied physics, but it also compares very well to journals in other field of physics. The impact factor of a journal gives an account of how often an average paper in the journal is referred to, in a two year time span after publication. The current impact factor of 2.59 is based on an evaluation conducted in 2005 of Laser and Particle Beams publications of 2003 and 2004. During the evaluation period (2005), Laser and Particle Beams publications were cited about 1000 times. The topics that attracted most attention were Fast Ignition (Deutsch, 2004; Mulser & Schneider, 2004a; Hora, 2004; Mulser & Bauer, 2004b), Inertial Fusion Targets (Borisenko et al., 2003), and Ion and Electron Acceleration in laser plasma and Ultrashort Pulses (Shorokhov & Pukhov, 2004; Osman et al., 2004; Malka & Fritzler, 2004; Limpouch et al., 2004; Pegoraro et al., 2004). However, the editorial boards of Laser and Particle Beams strongly encourage authors to submit their results in High Energy Density Physics, the emerging field of Warm Dense Matter, Pulsed Power and Accelerator Physics and Technology.

scholarly journals Characteristics and Trends of Research on New Energy Vehicle Reliability Based on the Web of Science

2018 ◽  
Vol 10 (10) ◽  
pp. 3560 ◽  
Author(s):  
Xian Zhao ◽  
Siqi Wang ◽  
Xiaoyue Wang
Keyword(s):  
Electric Vehicle ◽  
Energy Demand ◽  
High Performance ◽  
High Energy ◽  
Research Field ◽  
High Energy Density ◽  
Future Research ◽  
Charging System ◽  
New Energy ◽  
New Energy Vehicle

In order to satisfy the increasing energy demand and deal with the environmental problem caused by the conventional energy vehicle; the new energy vehicle (NEV), especially the electric vehicle (EV), has attracted increasing attention and the corresponding research has developed rapidly in recent years. The electric vehicle requires a battery with high energy density and frequent charging. In order to ensure high performance of the electric vehicle; the reliability of its charging system is extremely important. In this paper; an overview of the research on electric vehicle charging system reliability from 1998 to 2017 is presented from a bibliometric perspective. This study provides a comprehensive analysis of the current research climate and the emerging trends from the following four aspects: basic characteristics of publication outputs; including annual publication outputs and document types; collaboration analysis of countries/territories; institutions and authors; co-citation analysis of cited authors and cited references; co-occurrence analysis of subjects and keywords. By using CiteSpace; the collaboration relationship; co-citation and co-occurrence networks are shown clearly. According to the analysis results; studies in this research field will keep developing rapidly in the near future and several future research directions are proposed in the conclusions.

scholarly journals Citrullination regulates wound responses and tissue regeneration in zebrafish

2019 ◽  
Author(s):  
Netta Golenberg ◽  
Jayne M. Squirrell ◽  
David A. Bennin ◽  
Julie Rindy ◽  
Paige E. Pistono ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Tissue Regeneration ◽  
Protein Function ◽  
Tissue Injury ◽  
Post Translational Modification ◽  
Early Step ◽  
Calcium Dependent ◽  
Efficient Regeneration ◽  
Wound Responses ◽  
Histone Citrullination

AbstractCalcium signaling is an important early step in wound healing, yet how these early signals promote regeneration remains unclear. Peptidylarginine deiminases (PADs), a family of calcium-dependent enzymes, catalyze citrullination, a post-translational modification that alters protein function and has been implicated in autoimmune diseases. We generated a mutation in the single zebrafish ancestral pad gene, padi2, resulting in a loss of detectable calcium-dependent citrullination. The padi2 mutants exhibit impaired resolution of inflammation and regeneration after caudal fin transection. Further, we identified a new subpopulation of cells displaying citrullinated histones within the notochord bead following tissue injury. Citrullination of histones in this region was absent and wound-induced proliferation was perturbed in Padi2-deficient larvae. Taken together, our results show that Padi2 is required for the citrullination of histones within a group of cells in the notochord bead, and for promoting wound-induced proliferation required for efficient regeneration. These findings identify Padi2 as a potential intermediary between early calcium signaling and subsequent tissue regeneration.SummaryGolenberg et al. developed a citrullination-deficient zebrafish and demonstrated a role for Padi2 in fin wound responses and regeneration. This work identified a distinct population of cells within the regenerative notochord bead that exhibited wound-induced histone citrullination.

scholarly journals iProteinDB: an integrative database of Drosophila post-translational modifications

2018 ◽  
Author(s):  
Yanhui Hu ◽  
Richelle Sopko ◽  
Verena Chung ◽  
Romain A. Studer ◽  
Sean D. Landry ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Large Scale ◽  
Model Organisms ◽  
General Strategy ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Functional Sites ◽  
Evolutionarily Conserved ◽  
And Function

AbstractPost-translational modification (PTM) serves as a regulatory mechanism for protein function, influencing stability, protein interactions, activity and localization, and is critical in many signaling pathways. The best characterized PTM is phosphorylation, whereby a phosphate is added to an acceptor residue, commonly serine, threonine and tyrosine. As proteins are often phosphorylated at multiple sites, identifying those sites that are important for function is a challenging problem. Considering that many phosphorylation sites may be non-functional, prioritizing evolutionarily conserved phosphosites provides a general strategy to identify the putative functional sites with regards to regulation and function. To facilitate the identification of conserved phosphosites, we generated a large-scale phosphoproteomics dataset from Drosophila embryos collected from six closely-related species. We built iProteinDB (https://www.flyrnai.org/tools/iproteindb/), a resource integrating these data with other high-throughput PTM datasets, including vertebrates, and manually curated information for Drosophila. At iProteinDB, scientists can view the PTM landscape for any Drosophila protein and identify predicted functional phosphosites based on a comparative analysis of data from closely-related Drosophila species. Further, iProteinDB enables comparison of PTM data from Drosophila to that of orthologous proteins from other model organisms, including human, mouse, rat, Xenopus laevis, Danio rerio, and Caenorhabditis elegans.

Abstract 15523: Dynamic Protein S-palmitoylation Contributes to Cardiac Remodeling During Aging With Chronic Hypertension

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Madeleine R Miles ◽  
John Seo ◽  
Zachary Wilson ◽  
Min Jiang ◽  
Gea-ny Tseng
Keyword(s):  
Heart Failure ◽  
Protein Function ◽  
Ventricular Myocytes ◽  
Wide Spectrum ◽  
Enrichment Analysis ◽  
Protein S ◽  
Ventricular Myocardium ◽  
Chronic Hypertension ◽  
Post Translational Modification ◽  
Α Subunit

Introduction: More that 10% of human proteins can be S-palmitoylated, a post-translational modification (PTM) whereby palmitoyl chains are covalently linked to cysteine thiol groups. S-palmitoylation influences protein trafficking, distribution and function. There is no information on the scope of protein S-palmitoylation in the heart, or how this enzyme-mediated reversible PTM is regulated. Hypothesis: S-palmitoylation occurs to a wide spectrum of proteins in cardiomyocytes, and is coordinated by membrane-embedded palmitoylating (DHHC) enzymes. DHHC enzymes are subject to remodeling during chronic hypertension. Methods: We used resin-assisted capture to purify S-palmitoylated proteins from ventricular myocardium of 3 species: human, dog, and rat. We used global unbiased proteomic search to identify S-palmitoylated proteins. We validated DHHC antibodies and used them to monitor protein level and subcellular distribution of native DHHC enzymes in ventricular myocytes. Results: We built a 'composite' cardiac palmitome composed of 462 S-palmitoylatable proteins identified in ≥ 2 species-specific cardiac palmitomes. Enrichment analysis based on GO term 'cellular component' indicated that they are mainly involved in cell-cell and cell-substrate associations, sarcolemma and sarcomere organization, vesicular trafficking, G-protein function, ATP-dependent transmembrane transport, and mitochondria inner and outer membrane organization. Among the 23 DHHC enzymes, we detected ten in hearts across species. In ventricular myocytes with well-defined subcellular compartments, DHHC enzymes exhibited distinct distribution patterns: peripheral sarcolemma (DHHC1), M-lines (DHHC2), Z-lines (DHHC5), vesicles (DHHC7) and intercalated disc (DHHC9). In aging spontaneously hypertensive rats (a model of chronic hypertension, some in heart failure), seven DHHC enzymes were upregulated in the heart, accompanied by a higher degree of S-palmitoylation of CaMK II, caveolin3, Na/Ca exchanger, and Na/K pump α-subunit. Conclusion: S-palmitoylation is involved in most, if not all, aspects of cardiomyocyte function. Palmitoylation dysregulation may contribute to pathological progression in hypertrophy leading to heart failure.

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