scholarly journals Burkholderia PglL enzymes are serine preferring oligosaccharidetransferases which target conserved proteins across the Burkholderia genus

2021 ◽  
Author(s):  
Andrew J. Hayes ◽  
Jessica M. Lewis ◽  
Mark R. Davies ◽  
Nichollas E. Scott

AbstractGlycosylation is increasingly recognised as a common protein modification within bacterial proteomes. While great strides have been made in identifying species that contain glycosylation systems, our understanding of the proteins and sites targeted by these enzymes is far more limited. Within this work we explore the conservation of glycoproteins and O-linked glycosylation sites across the pan-Burkholderia glycoproteome. Using a multi-protease glycoproteomic approach we generate high-confidence glycoproteomes and associated glycosylation sites in two widely utilized B. cenocepacia strains, K56-2 and H111. This resource reveals glycosylation occurs exclusively at serine residues and that glycoproteins/glycosylation sites are highly conserved across 294 publicly available B. cenocepacia genomes. Consistent with this we demonstrate that the substitution of Serine for Threonine residues in a model protein results in a dramatic decrease in glycosylation efficiency by the oligosaccharidetransferase pglLBC even when pglLBC is overexpressed. This preference for glycosylation at Serine residues is observed across at least 9 Burkholderia glycoproteomes supporting that Serine is the dominant residue targeted by pglL-mediated glycosylation across the Burkholderia genus. Using population genomics we observe that pglL targeted glycosylated proteins are common across Burkholderia species. Combined, this work demonstrates that PglL enzymes of the Burkholderia genus are Serine-preferring oligosaccharidetransferases that target conserved and shared protein substrates across the Burkholderia genus.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Andrew J. Hayes ◽  
Jessica M. Lewis ◽  
Mark R. Davies ◽  
Nichollas E. Scott

AbstractGlycosylation is increasingly recognised as a common protein modification within bacterial proteomes. While great strides have been made in identifying species that contain glycosylation systems, our understanding of the proteins and sites targeted by these systems is far more limited. Within this work we explore the conservation of glycoproteins and glycosylation sites across the pan-Burkholderia glycoproteome. Using a multi-protease glycoproteomic approach, we generate high-confidence glycoproteomes in two widely utilized B. cenocepacia strains, K56-2 and H111. This resource reveals glycosylation occurs exclusively at Serine residues and that glycoproteins/glycosylation sites are highly conserved across B. cenocepacia isolates. This preference for glycosylation at Serine residues is observed across at least 9 Burkholderia glycoproteomes, supporting that Serine is the dominant residue targeted by PglL-mediated glycosylation across the Burkholderia genus. Combined, this work demonstrates that PglL enzymes of the Burkholderia genus are Serine-preferring oligosaccharyltransferases that target conserved and shared protein substrates.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiaofei Zhou ◽  
Shao-Cong Sun

AbstractCancer immunotherapy has become an attractive approach of cancer treatment with tremendous success in treating various advanced malignancies. The development and clinical application of immune checkpoint inhibitors represent one of the most extraordinary accomplishments in cancer immunotherapy. In addition, considerable progress is being made in understanding the mechanism of antitumor immunity and characterizing novel targets for developing additional therapeutic approaches. One active area of investigation is protein ubiquitination, a post-translational mechanism of protein modification that regulates the function of diverse immune cells in antitumor immunity. Accumulating studies suggest that E3 ubiquitin ligases and deubiquitinases form a family of potential targets to be exploited for enhancing antitumor immunity in cancer immunotherapy.


2021 ◽  
Author(s):  
Enrico Massignani ◽  
Roberto Giambruno ◽  
Marianna Maniaci ◽  
Luciano Nicosia ◽  
Avinash Yadav ◽  
...  

Protein Arginine (R) methylation is a post-translational modification involved in various biological processes, such as RNA splicing, DNA repair, immune response, signal transduction, and tumour development. Although several advancements were made in the study of this modification by mass spectrometry, researchers still face the problem of a high false discovery rate. We present a dataset of high-quality methylations obtained from several different heavy methyl SILAC (hmSILAC) experiments analysed with a machine learning-based tool doublets and show that this model allows for improved high-confidence identification of real methyl-peptides. Overall, our results are consistent with the notion that protein R methylation modulates protein:RNA interactions and suggest a role in rewiring protein:protein interactions, for which we provide experimental evidence for a representative case (i.e. NONO:PSPC1). Upon intersecting our R-methyl-sites dataset with a phosphosites dataset, we observed that R methylation correlates differently with S/T-Y phosphorylation in response to various stimuli. Finally, we explored the application of hmSILAC to identify unconventional methylated residues and successfully identified novel histone methylation marks on Serine 28 and Threonine 32 of H3.


2020 ◽  
Author(s):  
Cassandra M. Joiner ◽  
Forrest A. Hammel ◽  
John Janetzko ◽  
Suzanne Walker

ABSTRACTGlycosylation of nuclear and cytoplasmic proteins is an essential post-translational modification in mammals. O-GlcNAc transferase (OGT), the sole enzyme responsible for this modification, glycosylates over a thousand unique nuclear and cytoplasmic substrates. How OGT selects its substrates is a fundamental question that must be answered to understand OGT’s unusual biology. OGT contains a long tetratricopeptide repeat (TPR) domain that has been implicated in substrate selection, but there is almost no information about how changes to this domain affect glycosylation of individual substrates. Here, we used proteome-wide glycosylation profiling and probed glycosylation of selected purified substrates to show that asparagine and aspartate ladders that extend the full length of OGT’s TPR lumen control substrate glycosylation. We also found that substrates with glycosylation sites close to the C-terminus bypass lumenal binding. Our findings demonstrate that substrates can engage OGT in a variety of different ways for glycosylation.


Author(s):  
Aaron P. Ragsdale ◽  
Dominic Nelson ◽  
Simon Gravel ◽  
Jerome Kelleher

AbstractSimulation plays a central role in population genomics studies. Recent years have seen rapid improvements in software efficiency that make it possible to simulate large genomic regions for many individuals sampled from large numbers of populations. As the complexity of the demographic models we study grows, however, there is an ever-increasing opportunity to introduce bugs in their implementation. Here we describe two errors made in defining population genetic models using the msprime coalescent simulator that have found their way into the published record. We discuss how these errors have affected downstream analyses and give recommendations for software developers and users to reduce the risk of such errors.


1991 ◽  
Vol 275 (2) ◽  
pp. 529-534 ◽  
Author(s):  
I B Wilson ◽  
Y Gavel ◽  
G von Heijne

To study the sequence requirements for addition of O-linked N-acetylgalactosamine to proteins, amino acid distributions around 174 O-glycosylation sites were compared with distributions around non-glycosylated sites. In comparison with non-glycosylated serine and threonine residues, the most prominent feature in the vicinity of O-glycosylated sites is a significantly increased frequency of proline residues, especially at positions -1 and +3 relative to the glycosylated residues. Alanine, serine and threonine are also significantly increased. The high serine and threonine content of O-glycosylated regions is due to the presence of clusters of several closely spaced glycosylated hydroxy amino acids in many O-glycosylated proteins. Such clusters can be predicted from the primary sequence in some cases, but there is no apparent possibility of predicting isolated O-glycosylation sites from primary sequence data.


Author(s):  
Lachlan J. Gunn ◽  
François Chapeau-Blondeau ◽  
Mark D. McDonnell ◽  
Bruce R. Davis ◽  
Andrew Allison ◽  
...  

Is it possible for a large sequence of measurements or observations, which support a hypothesis, to counterintuitively decrease our confidence? Can unanimous support be too good to be true? The assumption of independence is often made in good faith; however, rarely is consideration given to whether a systemic failure has occurred. Taking this into account can cause certainty in a hypothesis to decrease as the evidence for it becomes apparently stronger. We perform a probabilistic Bayesian analysis of this effect with examples based on (i) archaeological evidence, (ii) weighing of legal evidence and (iii) cryptographic primality testing. In this paper, we investigate the effects of small error rates in a set of measurements or observations. We find that even with very low systemic failure rates, high confidence is surprisingly difficult to achieve; in particular, we find that certain analyses of cryptographically important numerical tests are highly optimistic, underestimating their false-negative rate by as much as a factor of 2 80 .


2021 ◽  
Author(s):  
Yixin Ma ◽  
Shunyu Ning ◽  
Nan Song ◽  
Si Chen ◽  
Xue Leng ◽  
...  

Abstract Background: Ginsenoside Rb1, known as Renshen in traditional Chinese medicine, is one of the major bioactive saponins isolated from Panax ginseng C.A.Mey. N-glycosylation is the most common type of post-translational modification in cells. The widespread localization of N-glycosylated proteins (N-glycoproteins) between extracellular spaces and on the cell surfaces give them unique advantages as disease biomarkers and drug targets. Previous study found that Ginsenoside Rb1 could potentially play a preventive role in hyperlipidemia. This study aims to reveal the hypolipidemic effect at the protein modification level. Methods: 24 male SD rats were randomly devided into 3 groups: control group (CON), high fat diet group (HFD) and Ginsenoside Rb1 group (Rb1). Both HFD and Rb1 groups were fed with high-fat diet for 12 weeks. The Rb1 group started intragastric administering Ginsenoside Rb1 200 mg·kg -1 ·d -1 at 5th week for 8 weeks, while the CON and HFD group the same amount of normal saline for the same amount of time. Lipid levels and liver histology were assayed to evaluate the effects of Ginsenoside Rb1 intake on hyperlipidemia rats. Furthermore, the workflow by combination of isotope TMT labeling, HILIC enrichment, and high-resolution LC-MS/MS analysis were employed to exploring the mechanisms of regulation role in hyperlipidemia rats.Results: The histopathologic characteristics and biochemical data shows that Ginsenoside Rb1 exhibited regulative effects on hyperlipidemia rats. After being analyzed by N-glycoproteomic, 98 differential N-glycosylation sites on 53 glycoproteins between 2 comparison groups (HFD: CON, Rb1: HFD) were identified. Analyses of N-glycosylation sites distribution found that albumin (Alb) and Serpinc1 were most heavily modified with 6 N-glycosylation sites changed in this work. GO enrichment analysis showed that differential modified glycoproteins were involved in inflammatory response, cellular iron ion homeostasis and positive regulation of cholesterol efflux etc. biosynthetic process. Complement and coagulation cascades was the most significant enriched in the KEGG pathway enrichment analysis. Conclusions: This study presents a comprehensive analysis of a new set of N-glycoproteins which are altered by Ginsenoside Rb1 and offers some valuable clues for novel mechanistic insights into the ragulative mechanism of Ginsenoside Rb1. Results from N-glycoproteomic suggest that to suppress hyperlipidemia, Rb1 may regulates N-glycosylation of Alb, Serpinc1, PON1, Lrp1, Cp and THBS1, as well as differentially modified glycoproteins in complement and coagulation cascades, which in turn improve the imbalance of lipid homeostasis.


2012 ◽  
Vol 393 (4) ◽  
pp. 291-298 ◽  
Author(s):  
Jolien Hollebeke ◽  
Petra Van Damme ◽  
Kris Gevaert

Abstract Protein N-terminal acetylation by Nα-acetyltransferases (NATs) is an omnipresent protein modification that affects a large number of proteins. The exact biological role of N-terminal acetylation has, however, remained enigmatic for the overall majority of affected proteins, and only for a rather small number of proteins, N-terminal acetylation was linked to various protein features including stability, localization, and interactions. This minireview tries to summarize the recent progress made in understanding the functionality of N-terminal protein acetylation and also focuses on noncanonical functions of the NATs subunits.


Sign in / Sign up

Export Citation Format

Share Document