scholarly journals Profiling the reactivity of cyclic C-nucleophiles towards electrophilic sulfur in cysteine sulfenic acid

2016 ◽  
Vol 7 (1) ◽  
pp. 400-415 ◽  
Author(s):  
Vinayak Gupta ◽  
Kate S. Carroll
Keyword(s):  
Protein Function ◽  
Crucial Role ◽  
Post Translational Modification ◽  
Sulfenic Acid ◽  
Disease States

Oxidation of a protein cysteine thiol to sulfenic acid, termed S-sulfenylation, is a reversible post-translational modification that plays a crucial role in regulating protein function and is correlated with disease states.

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 The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erna Davydova ◽  
Tadahiro Shimazu ◽  
Maren Kirstin Schuhmacher ◽  
Magnus E. Jakobsson ◽  
Hanneke L. D. M. Willemen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Crucial Role ◽  
Complex I ◽  
Protein Modification ◽  
Zinc Binding ◽  
Functional Studies ◽  
Mitochondrial Respiratory Complex ◽  
Respiratory Complex I ◽  
Broad Specificity

AbstractPost-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where “x” is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.

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.

scholarly journals Chemical Decorations of “MARs” Residents in Orchestrating Eukaryotic Gene Regulation

2020 ◽  
Vol 8 ◽  
Author(s):  
Tanaya Roychowdhury ◽  
Samit Chattopadhyay
Keyword(s):  
Gene Regulation ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Protein Function ◽  
Functional Outcomes ◽  
Three Dimensional ◽  
Limited Information ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
3D Matrix

Genome organization plays a crucial role in gene regulation, orchestrating multiple cellular functions. A meshwork of proteins constituting a three-dimensional (3D) matrix helps in maintaining the genomic architecture. Sequences of DNA that are involved in tethering the chromatin to the matrix are called scaffold/matrix attachment regions (S/MARs), and the proteins that bind to these sequences and mediate tethering are termed S/MAR-binding proteins (S/MARBPs). The regulation of S/MARBPs is important for cellular functions and is altered under different conditions. Limited information is available presently to understand the structure–function relationship conclusively. Although all S/MARBPs bind to DNA, their context- and tissue-specific regulatory roles cannot be justified solely based on the available information on their structures. Conformational changes in a protein lead to changes in protein–protein interactions (PPIs) that essentially would regulate functional outcomes. A well-studied form of protein regulation is post-translational modification (PTM). It involves disulfide bond formation, cleavage of precursor proteins, and addition or removal of low-molecular-weight groups, leading to modifications like phosphorylation, methylation, SUMOylation, acetylation, PARylation, and ubiquitination. These chemical modifications lead to varied functional outcomes by mechanisms like modifying DNA–protein interactions and PPIs, altering protein function, stability, and crosstalk with other PTMs regulating subcellular localizations. S/MARBPs are reported to be regulated by PTMs, thereby contributing to gene regulation. In this review, we discuss the current understanding, scope, disease implications, and future perspectives of the diverse PTMs regulating functions of S/MARBPs.

Cell signalling by oxidized lipids and the role of reactive oxygen species in the endothelium

2005 ◽  
Vol 33 (6) ◽  
pp. 1385-1389 ◽  
Author(s):  
J.W. Zmijewski ◽  
A. Landar ◽  
N. Watanabe ◽  
D.A. Dickinson ◽  
N. Noguchi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Oxidation ◽  
Protein Function ◽  
Cell Signalling ◽  
Reactive Oxygen ◽  
Oxidation Products ◽  
Oxidized Lipids ◽  
Oxygen Species ◽  
Post Translational Modification ◽  
Lipid Oxidation Products

The controlled formation of ROS (reactive oxygen species) and RNS (reactive nitrogen species) is now known to be critical in cellular redox signalling. As with the more familiar phosphorylation-dependent signal transduction pathways, control of protein function is mediated by the post-translational modification at specific amino acid residues, notably thiols. Two important classes of oxidant-derived signalling molecules are the lipid oxidation products, including those with electrophilic reactive centres, and decomposition products such as lysoPC (lysophosphatidylcholine). The mechanisms can be direct in the case of electrophiles, as they can modify signalling proteins by post-translational modification of thiols. In the case of lysoPC, it appears that secondary generation of ROS/RNS, dependent on intracellular calcium fluxes, can cause the secondary induction of H2O2 in the cell. In either case, the intracellular source of ROS/RNS has not been defined. In this respect, the mitochondrion is particularly interesting since it is now becoming apparent that the formation of superoxide from the respiratory chain can play an important role in cell signalling, and oxidized lipids can stimulate ROS formation from an undefined source. In this short overview, we describe recent experiments that suggest that the cell signalling mediated by lipid oxidation products involves their interaction with mitochondria. The implications of these results for our understanding of adaptation and the response to stress in cardiovascular disease are discussed.

Novel Sites of Gamma Carboxylation in Human Factor VII

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3759-3759
Author(s):  
Emily M Wilkerson ◽  
Barbara Bates ◽  
Kraig T Kumfer ◽  
Nicholas M Riley ◽  
Brad S Schwartz ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electron Transfer ◽  
Protein Function ◽  
Synthetic Peptides ◽  
Conflicts Of Interest ◽  
Coagulation Factor ◽  
Factor Vii ◽  
Post Translational Modification ◽  
Coagulation Factor Vii ◽  
Gla Domain

Abstract Introduction Gamma- (γ-) carboxylation of glutamate residues is a vitamin K-dependent post-translational modification critical to the function of several plasma proteins. Found in the N-terminal domains of specific proteins, most of which are involved in hemostasis, these γ-carboxyglutamate residues (Gla) help mediate binding of divalent cations and are essential to protein function. Coagulation factor VII(a) bears 10 known Gla residues as characterized by N-terminal sequencing, yet Thim et al.( Biochemistry 27:7785 1988) used amino acid analysis to quantify 11.0 mol of Gla/mol of protein for plasma-derived factor VII(a). We used mass spectrometry to map and validate Gla residues of coagulation factor VII(a) to potentially identify Gla residues outside of the Gla domain. Methods Four sources of factor VII(a) (2 plasma-derived and 2 recombinant) were extracted, digested, and analyzed by tandem mass spectrometry (LC-MS/MS). Each sample was digested with trypsin and chymotrypsin to provide orthogonal coverage. Peptides derived from factor VII(a) proteolysis were analyzed on a nanoLC coupled to a quadrupole-Orbitrap-quadrupole linear ion trap mass spectrometer (Orbitrap Fusion Lumos Thermo Scientific). Multiple fragmentation methods were used to map and validate the sites including collisional based dissociation (CAD), higher energy collisional activated dissociation (HCD), electron transfer dissociation (ETD), and electron-transfer/higher-energy electron transfer activation (EThcD). Tandem MS spectra were collected at resolution 30K at 200 m/z, and data were processed using MaxQuant, COMPASS, and Proteome Discoverer. All identified sites were validated through manual annotation of spectra. We estimate that any site with >1% occupancy will be identified as Gla with this method. To validate select sites of novel gamma carboxylation, synthetic peptides were made for 4 different sites that were consistently identified in factor VII(a) from all 4 sources. Synthetic peptides were analyzed using MS methods described above, generating "true positives" to match with peptides identified from the factor VII(a) sources. Spectra from the synthetic peptides and factor VII from each source were compared using manual spectral annotation. Results In addition to identifying known Gla residues at positions 6, 7, 19, 20, 29, and 35 of factor VII(a), we detected and validated 9 novel Gla residues outside of the N-terminal Gla domain. Novel sites include residues 94, 116, 132, 219, 215, 229, 265, 196 and 385. Four of these residues (210, 220, 296 and 385) were identified as Gla in all 4 sources of factor VII(a) and were validated with synthetic peptides using a combination of fragmentation methods, providing high confidence in their characterization. Published crystallographic data suggest that residues 210 and 220 of factor VIIa-tissue factor are closely approximated to a Ca2+ ion complexed to the C-terminal protease domain; this is not the case for residues 296 and 385. We continue to refine the technique to map the Gla residues (novel and known), and to quantify the fraction of factor VII(a) molecules from each source that contain the modification at each site, in order to better incorporate our data with established studies showing >90% occupancy at each of the 10 Gla domain sites. These data suggest there is room to expand our understanding of how carboxylation contributes to specific protein function, in order to provide more comprehensive understanding of this post-translational modification, and refine our understanding of hemostatic mechanisms. Disclosures No relevant conflicts of interest to declare.

scholarly journals SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress

Open Biology ◽  
2013 ◽  
Vol 3 (10) ◽  
pp. 120173 ◽  
Author(s):  
Ingrid Kassner ◽  
Anneli Andersson ◽  
Monika Fey ◽  
Martin Tomas ◽  
Elisa Ferrando-May ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Interactions ◽  
Protein Function ◽  
Dependent Manner ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Target Proteins ◽  
Protein Methyltransferase

ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) is localized in the nucleus, where it ADP-ribosylates specific target proteins. The post-translational modification (PTM) with a single ADP-ribose unit or with polymeric ADP-ribose (PAR) chains regulates protein function as well as protein–protein interactions and is implicated in many biological processes and diseases. SET7/9 (Setd7, KMT7) is a protein methyltransferase that catalyses lysine monomethylation of histones, but also methylates many non-histone target proteins such as p53 or DNMT1. Here, we identify ARTD1 as a new SET7/9 target protein that is methylated at K508 in vitro and in vivo . ARTD1 auto-modification inhibits its methylation by SET7/9, while auto-poly-ADP-ribosylation is not impaired by prior methylation of ARTD1. Moreover, ARTD1 methylation by SET7/9 enhances the synthesis of PAR upon oxidative stress in vivo . Furthermore, laser irradiation-induced PAR formation and ARTD1 recruitment to sites of DNA damage in a SET7/9-dependent manner. Together, these results reveal a novel mechanism for the regulation of cellular ARTD1 activity by SET7/9 to assure efficient PAR formation upon cellular stress.

Sign in / Sign up

Export Citation Format

Share Document