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1.
Lantibiotics are a subgroup of bacteriocins that are characterized by the presence of the unusual thioether amino acids lanthionine and 3‐methyllanthionine generated through posttranslational modification. The biosynthesis of lantibiotics follows a defined pathway comprising modifications of the prepeptide, proteolytic activation, and export. The genes encoding the biosynthesis apparatus and the lantibiotic prepeptide are organized in clusters, which also include information for proteins involved in regulation and producer self‐protection. The elongated cationic lantibiotics primarily act through the formation of pores and recent progress with nisin and epidermin has shown that specific docking molecules such as lipid II play an essential role in this mechanism. Mersacidin and actagardine inhibit cell wall biosynthesis by complexing the precursor lipid II, whereas the cinnamycin‐like peptides bind to phosphoethanolamine thus inhibiting phospholipase A2. © 2000 John Wiley & Sons, Inc. Biopoly 55: 62–73, 2000 相似文献
2.
Boros S Ahrman E Wunderink L Kamps B de Jong WW Boelens WC Emanuelsson CS 《Proteins》2006,62(4):1044-1052
Crosslinking of small heat-shock proteins (sHsps) by tissue transglutaminase (tTG) is enhanced by stress and under pathological conditions. We here used hexapeptide probes to determine the amine donor (K) and acceptor (Q) sites for tTG in Hsp20. Mass spectrometric peptide mass fingerprinting and peptide fragmentation established that Q31 and the C-terminal K162 are involved in inter- and intramolecular crosslinking (transamidation). Q31 is a conserved glutamine in sHsps where the neighboring residue determines its reactivity. Moreover, we detected highly efficient simultaneous deamidation of Q66, which suggests that tTG-catalyzed transamidation and deamidation is specific for different glutamine residues. 相似文献
3.
Yangchun Xie Rui Kang Xiaofang Sun Meizuo Zhong Jin Huang Daniel J. Klionsky Daolin Tang 《Autophagy》2015,11(1):28-45
Macroautophagy is an intracellular catabolic process involved in the formation of multiple membrane structures ranging from phagophores to autophagosomes and autolysosomes. Dysfunction of macroautophagy is implicated in both physiological and pathological conditions. To date, 38 autophagy-related (ATG) genes have been identified as controlling these complicated membrane dynamics during macroautophagy in yeast; approximately half of these genes are clearly conserved up to human, and there are additional genes whose products function in autophagy in higher eukaryotes that are not found in yeast. The function of the ATG proteins, in particular their ability to interact with a number of macroautophagic regulators, is modulated by posttranslational modifications (PTMs) such as phosphorylation, glycosylation, ubiquitination, acetylation, lipidation, and proteolysis. In this review, we summarize our current knowledge of the role of ATG protein PTMs and their functional relevance in macroautophagy. Unraveling how these PTMs regulate ATG protein function during macroautophagy will not only reveal fundamental mechanistic insights into the regulatory process, but also provide new therapeutic targets for the treatment of autophagy-associated diseases. 相似文献
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While the posttranslational N-terminal arginylation of proteins has been demonstrated in a variety of eukaryotic cells including neurons and their axons, the targets of the reaction are poorly understood. Several lines of evidence suggest that arginylation may be a cytoprotective mechanism used by cells to target oxidatively damaged (and thus potentially toxic) proteins for degradation. In the present experiments, we have begun to test this hypothesis by incubating oxidized test proteins in a rat brain extract capable of arginylating endogenous proteins. Bovine serum albumin, pancreatic ribonuclease-A and the A-chain of insulin were chosen as test proteins and either oxidized by metal catalyzed oxidation or purchased in their oxidized forms and incubated with the extract and [3H]Arg. SDS PAGE of the incubation product showed [3H]Arg migrating with the oxidized forms of BSA and RNase but not with the un-oxidized form of BSA. Following incubation with the oxidized A-chain of insulin, analysis of the [3H]product by SDS PAGE and HPLC showed co-migration of [3H]Arg with A-chain standards and amino acid sequencing showed [3H]Arg at the N-terminus of the A-chain of insulin. The data suggest that oxidative damage to a protein may be a signal for its N-terminal arginylation. 相似文献
6.
《Autophagy》2013,9(1):28-45
Macroautophagy is an intracellular catabolic process involved in the formation of multiple membrane structures ranging from phagophores to autophagosomes and autolysosomes. Dysfunction of macroautophagy is implicated in both physiological and pathological conditions. To date, 38 autophagy-related (ATG) genes have been identified as controlling these complicated membrane dynamics during macroautophagy in yeast; approximately half of these genes are clearly conserved up to human, and there are additional genes whose products function in autophagy in higher eukaryotes that are not found in yeast. The function of the ATG proteins, in particular their ability to interact with a number of macroautophagic regulators, is modulated by posttranslational modifications (PTMs) such as phosphorylation, glycosylation, ubiquitination, acetylation, lipidation, and proteolysis. In this review, we summarize our current knowledge of the role of ATG protein PTMs and their functional relevance in macroautophagy. Unraveling how these PTMs regulate ATG protein function during macroautophagy will not only reveal fundamental mechanistic insights into the regulatory process, but also provide new therapeutic targets for the treatment of autophagy-associated diseases. 相似文献
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Zhixin Tian Nikola Toli? Rui Zhao Ronald J Moore Shawna M Hengel Errol W Robinson David L Stenoien Si Wu Richard D Smith Ljiljana Pa?a-Toli? 《Genome biology》2012,13(10):R86
Post-translational modifications (PTMs) of core histones work synergistically to fine tune chromatin structure and function, generating a so-called histone code that can be interpreted by a variety of chromatin interacting proteins. We report a novel online two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) platform for high-throughput and sensitive characterization of histone PTMs at the intact protein level. The platform enables unambiguous identification of 708 histone isoforms from a single 2D LC-MS/MS analysis of 7.5 µg purified core histones. The throughput and sensitivity of comprehensive histone modification characterization is dramatically improved compared with more traditional platforms. 相似文献
9.
Fatma Asli Erdem Isabella Salzer Wei‐Qiang Chen Gangsoo Jung Gert Lubec Stefan Boehm Jae‐Won Yang 《Proteomics》2017,17(19)
Voltage‐gated Kv7.2 potassium channels regulate neuronal excitability. The gating of these channels is tightly controlled by various mediators and neurotransmitters acting via G protein‐coupled receptors; the underlying signaling cascades involve phosphatidylinositol‐4,5‐bisphosphate (PIP2), Ca2+/calmodulin, and phosphorylation. Recent studies found that the PIP2 sensitivity of Kv7.2 channels is affected by two posttranslational modifications, phosphorylation and methylation, harboured within putative PIP2‐binding domains. In this study, we updated phosphorylation and methylation sites in Kv7.2 either heterologously expressed in mammalian cells or as GST‐fusion proteins exposed to recombinant protein kinases by using LC–MS/MS. In vitro kinase assays revealed that CDK5, protein kinase C (PKC) alpha, PKA, p38 MAPK, CamKIIα, and GSK3β could mediate phosphorylation. Taken together, we provided a comprehensive map of phosphorylation and methylation in Kv7.2 within protein–protein and protein–lipid interaction domains. This may help to interpret the functional roles of individual PTM sites in Kv7.2 channels. All MS data are available via ProteomeXchange with the identifier PXD005567. 相似文献
10.
Environmentally induced flax genotrophs L and S show heritable shifts in the relative mobilities of peroxidase, esterase, and acid phosphatase isozymes, plus a number of nonspecific glycoproteins. All L isozymes migrated faster than corresponding S isozymes in 10% acrylamide gels. Various aspects of these shifts are reviewed here; it is proposed that posttranslational modification, probably of the carbohydrate moieties of these glycoproteins, underlies the shifts. This proposal is discussed in relation to the switch model for genotroph induction.The financial assistance of the Natural Sciences and Engineering Research Council of Canada is acknowledged with thanks. 相似文献
11.
ADP-ribosylation reactions in nucleoli of exponentially growing HeLa cells were studied. Isolated nuclei or nucleoli were labeled with 32P-NAD; then the nucleolar proteins were analyzed by 1-dimensional and 2-dimensional polyacrylamide gel electrophoresis (PAGE) and modified proteins were detected by autoradiography. The labeled nucleolar proteins were also chromatographically fractionated on DEAE-cellulose. Electrophoretic analysis of total nucleolar and chromatographically purified proteins revealed that besides nuclear ADP-ribosyltransferase and histones two characteristic nucleolar phosphoproteins numatrin/B23 and nucleolin/C23 were modified by ADP-ribosylation. 相似文献
12.
塑料广泛存在于人类的日常生活中,在给人们生活带来便利的同时,大量塑料废物也给环境带来很大压力。聚对苯二甲酸乙二醇酯(polyethylene terephthalate, PET)是一种以石油为原料的高分子热塑性材料,因其具有耐用、透明度高、重量轻等特性,已成为世界上使用最广泛的塑料之一。由于PET具有结构复杂以及难降解的特性,可在自然界中长期存在,不仅对全球生态环境造成严重的污染,而且已经威胁到人类健康。如何对PET废弃物进行降解已成为全球的难题之一,相较于物理法和化学法,生物降解法是目前处理PET废弃物最为绿色环保的方法。本文分别介绍了微生物和生物酶对PET生物降解的研究现状、PET的生物降解途径、PET生物降解机制以及PET降解酶的分子改造等方面的研究,并对如何实现PET的高效降解、寻找和改造可降解高结晶度PET的微生物或酶进行展望,为PET的生物降解微生物或酶的有效开发应用提供理论依据。 相似文献
13.
Jie Li Wenxia Ma Huizhong Li Ning Hou Xuejun Wang Il-man Kim Faqian Li Huabo Su 《The Journal of biological chemistry》2015,290(39):23850-23862
Neddylation is a posttranslational modification that controls diverse biological processes by covalently conjugating the ubiquitin-like protein NEDD8 to specific targets. Neddylation is commonly mediated by NEDD8-specific enzymes (typical neddylation) and, sometimes, by ubiquitin enzymes (atypical neddylation). Although typical neddylation is known to regulate protein function in many ways, the regulatory mechanisms and biological consequence of atypical neddylation remain largely unexplored. Here we report that NEDD8 conjugates were accumulated in the diseased hearts from mouse models and human patients. Proteotoxic stresses induced typical and atypical neddylation in cardiomyocytes. Loss of NUB1L exaggerated atypical neddylation, whereas NUB1L overexpression repressed atypical neddylation through promoting the degradation of NEDD8. Activation of atypical neddylation accumulated a surrogate misfolded protein, GFPu. In contrast, suppression of atypical neddylation by NUB1L overexpression enhanced GFPu degradation. Moreover, NUB1L depletion accumulated a cardiomyopathy-linked misfolded protein, CryABR120G, whereas NUB1L overexpression promoted its degradation through suppressing neddylation of ubiquitinated proteins in cardiomyocytes. Consequently, NUB1L protected cells from proteotoxic stress-induced cell injury. In summary, these data indicate that NUB1L suppresses atypical neddylation and promotes the degradation of misfolded proteins by the proteasome. Our findings also suggest that induction of NUB1L could potentially become a novel therapeutic strategy for diseases with increased proteotoxic stress. 相似文献
14.
With an exponential growth in applications identifying protein post‐translational modifications via mass spectrometry, discovery and presentation of motifs surrounding those modification sites have become increasingly desirable. Despite a few tools being designed, there is still a scarcity of effective and polyfunctional software for such analysis and illustrations. In this study, a versatile and user‐friendly web tool is developed, motifeR, for extracting and visualizing statistically significant motifs from large datasets. Particularly, several functions are also integrated for processing multi‐modification sites enrichment. Public datasets are applied to test their usability, indicating that some concurrent modification sites may form motifs and that peptides with low location probability may be not identified randomly and can be included to support motif discovery. In addition, for human phosphoproteomics datasets, the characterization of differential kinase signaling networks can be estimated and modeled by combining kinase‐substrate relations based on the NetworKIN database as an optional feature for users. The motifeR toolkit can be conveniently operated by any scientific community or individuals, even those without any bioinformatics background and is freely available at https://www.omicsolution.org/wukong/motifeR . 相似文献
15.
Mujun Yu Goutam Chakraborty Michael Grabow Nicholas A. Ingoglia 《Neurochemical research》1994,19(1):105-110
The tRNA mediated, posttranslational, N-terminal arginylation of proteins occurs in all eukaryotic cells. In nervous tissue, these reactions can be inhibited by endogenous molecules with a molecular weight of between one thousand and five thousand. In the present experiments, exogenous serine protease inhibitors (10–5M or less) but not other types of protease inhibitors, were found to be able to block the arginylation of protein in extracts of rat brain homogenates. Inhibition was not by the usual mode of action of protease inhibitors, but by interfering (non-competitively) with the charging of tRNA. Since arginylated proteins are rapidly ubiquitinated and degraded by cytosolic proteases, serine protease inhibitors may act to stabilize proteins by a dual mechanism of inhibiting arginylation as well as inhibiting serine proteases. 相似文献
16.
《Bioscience, biotechnology, and biochemistry》2013,77(11):2374-2387
Bacteria produce and respond to signal molecules depending on their cell density. This process is called “quorum sensing”. The ComX pheromone, controlled by quorum sensing, activates natural genetic competence in Bacillus subtilis. ComX is an oligopeptide with a posttranslational modification. It has been suggested that ComX pheromone is modified with an isoprenoid at its tryptophan residue, but the complete chemical structure is unknown. We first determined the molecular formula of ComXRO-E-2, a competence factor for B. subtilis strain RO-E-2. Then we synthesized putative pheromones with 1-, 2-, 4-, 5-, 6-, or 7-geranyl substituted tryptophan residues. The regio- and stereo-selective synthesis of the geranyl tryptophans was successful, and we prepared the six peptides with modified tryptophan residues. These peptides had the same molecular formula and showed similar hydrophobicity to the natural ComXRO-E-2 in LC–MS analysis. But, none of them showed the same retention time as the natural pheromone and none exhibited its biological activity. These results suggest that the isoprenoid modification pattern of the tryptophan residue is more complex than postulated. 相似文献
17.
Thomas F M Cummings Kevin Gori Luis Sanchez-Pulido Gavriil Gavriilidis David Moi Abigail R Wilson Elizabeth Murchison Christophe Dessimoz Chris P Ponting Maria A Christophorou 《Molecular biology and evolution》2022,39(2)
Protein posttranslational modifications add great sophistication to biological systems. Citrullination, a key regulatory mechanism in human physiology and pathophysiology, is enigmatic from an evolutionary perspective. Although the citrullinating enzymes peptidylarginine deiminases (PADIs) are ubiquitous across vertebrates, they are absent from yeast, worms, and flies. Based on this distribution PADIs were proposed to have been horizontally transferred, but this has been contested. Here, we map the evolutionary trajectory of PADIs into the animal lineage. We present strong phylogenetic support for a clade encompassing animal and cyanobacterial PADIs that excludes fungal and other bacterial homologs. The animal and cyanobacterial PADI proteins share functionally relevant primary and tertiary synapomorphic sequences that are distinct from a second PADI type present in fungi and actinobacteria. Molecular clock calculations and sequence divergence analyses using the fossil record estimate the last common ancestor of the cyanobacterial and animal PADIs to be less than 1 billion years old. Additionally, under an assumption of vertical descent, PADI sequence change during this evolutionary time frame is anachronistically low, even when compared with products of likely endosymbiont gene transfer, mitochondrial proteins, and some of the most highly conserved sequences in life. The consilience of evidence indicates that PADIs were introduced from cyanobacteria into animals by horizontal gene transfer (HGT). The ancestral cyanobacterial PADI is enzymatically active and can citrullinate eukaryotic proteins, suggesting that the PADI HGT event introduced a new catalytic capability into the regulatory repertoire of animals. This study reveals the unusual evolution of a pleiotropic protein modification. 相似文献
18.
随着分子生物学的研究和不断发展,基因表达技术有了很大的进步。到目前为止,人们已经研究出多种表达系统用以生产重组蛋白,但没有一种表达系统能够完全满足当前需要,各种活性肽和蛋白质类药物的需求逐年攀升,不仅对表达量有要求,更需要正确的翻译后折叠、修饰,使表达蛋白和天然构象更加接近,具有更高的活性和稳定性。结合目前的研究工作从表达系统与宿主、分泌表达、共表达、融合表达和培养条件等方面综述了其对重组蛋白正确折叠以及翻译后修饰的影响,并提出可能改进的策略。 相似文献
19.
邻苯二甲酸酯(Phthalates esters, PAEs)是一类混合在塑料中以增强其可塑性和多功能性的有机化合物。同时,PAEs也是一种典型环境内分泌干扰物,长期生产和使用塑料制品已对环境和生物体乃至人类身体健康造成危害。研究发现微生物降解已成为削减环境中PAEs的主要途径。文中对近年来国内外在PAEs的结构及分类、毒理学效应、在环境中的污染状况、细菌降解的菌株多样性、降解途径及分子机制等方面的相关研究进行了总结与回顾,以期对解决PAEs的污染问题提供参考。 相似文献
20.
Ohyama K Ogawa M Matsubayashi Y 《The Plant journal : for cell and molecular biology》2008,55(1):152-160
Peptidomics is a challenging field in which to create a link between genomic information and biological function through biochemical analysis of expressed peptides, including precise identification of post-translational modifications and proteolytic processing. We found that secreted peptides in Arabidopsis plants diffuse into the medium of whole-plant submerged cultures, and can be effectively identified by o- chlorophenol extraction followed by LC-MS analysis. Using this system, we first confirmed that a 12-amino-acid mature CLE44 peptide accumulated at a considerable level in the culture medium of transgenic plants overexpressing CLE44 . Next, using an in silico approach, we identified a novel gene family encoding small secreted peptides that exhibit significant sequence similarity within the C-terminal short conserved domain. We determined that the mature peptide encoded by At1g47485 , a member of this gene family, is a 15-amino-acid peptide containing two hydroxyproline residues derived from the conserved domain. This peptide, which we have named CEP1, is mainly expressed in the lateral root primordia and, when overexpressed or externally applied, significantly arrests root growth. CEP1 is a candidate for a novel peptide plant hormone. 相似文献