scholarly journals Histone lysine methacrylation is a dynamic post-translational modification regulated by HAT1 and SIRT2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Kyle Delaney ◽  
Minjia Tan ◽  
Zhesi Zhu ◽  
Jinjun Gao ◽  
Lunzhi Dai ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Metabolic Pathways ◽  
Histone Mark ◽  
Structural Isomer ◽  
Post Translational Modification ◽  
Site Specific ◽  
Affinity Enrichment ◽  
Histone Lysine ◽  
Biochemical Studies ◽  
New Type

AbstractHistone lysine crotonylation is a posttranslational modification with demonstrated functions in transcriptional regulation. Here we report the discovery of a new type of histone posttranslational modification, lysine methacrylation (Kmea), corresponding to a structural isomer of crotonyllysine. We validate the identity of this modification using diverse chemical approaches and further confirm the occurrence of this type of histone mark by pan specific and site-specific anti-methacryllysine antibodies. In total, we identify 27 Kmea modified histone sites in HeLa cells using affinity enrichment with a pan Kmea antibody and mass spectrometry. Subsequent biochemical studies show that histone Kmea is a dynamic mark, which is controlled by HAT1 as a methacryltransferase and SIRT2 as a de-methacrylase. Altogether, these investigations uncover a new type of enzyme-catalyzed histone modification and suggest that methacrylyl-CoA generating metabolism is part of a growing number of epigenome-associated metabolic pathways.

scholarly journals An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in humans

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Abbey D. Zuehlke ◽  
Michael Reidy ◽  
Coney Lin ◽  
Paul LaPointe ◽  
Sarah Alsomairy ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Site Specific ◽  
Chaperone Protein

scholarly journals Neutrophil azurophilic granule glycoproteins are distinctively decorated by atypical pauci- and phosphomannose glycans

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Karli R. Reiding ◽  
Yu-Hsien Lin ◽  
Floris P. J. van Alphen ◽  
Alexander B. Meijer ◽  
Albert J. R. Heck
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Secreted Proteins ◽  
Receptor Interaction ◽  
Post Translational Modification ◽  
Site Specific ◽  
Healthy Donors ◽  
Asymmetric Hybrid ◽  
Membrane Bound ◽  
High Mannose

AbstractWhile neutrophils are critical first-responders of the immune system, they also cause tissue damage and act in a variety of autoimmune diseases. Many neutrophil proteins are N-glycosylated, a post-translational modification that may affect, among others, enzymatic activity, receptor interaction, and protein backbone accessibility. So far, a handful neutrophil proteins were reported to be decorated with atypical small glycans (paucimannose and smaller) and phosphomannosylated glycans. To elucidate the occurrence of these atypical glycoforms across the neutrophil proteome, we performed LC-MS/MS-based (glyco)proteomics of pooled neutrophils from healthy donors, obtaining site-specific N-glycan characterisation of >200 glycoproteins. We found that glycoproteins that are typically membrane-bound to be mostly decorated with high-mannose/complex N-glycans, while secreted proteins mainly harboured complex N-glycans. In contrast, proteins inferred to originate from azurophilic granules carried distinct and abundant paucimannosylation, asymmetric/hybrid glycans, and glycan phosphomannosylation. As these same proteins are often autoantigenic, uncovering their atypical glycosylation characteristics is an important step towards understanding autoimmune disease and improving treatment.

scholarly journals Protein lysine 43 methylation by EZH1 promotes AML1-ETO transcriptional repression in leukemia

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Liping Dou ◽  
Fei Yan ◽  
Jiuxia Pang ◽  
Dehua Zheng ◽  
Dandan Li ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Transcriptional Repression ◽  
Lysine Methylation ◽  
Post Translational Modification ◽  
Histone Lysine Methylation ◽  
Histone Lysine ◽  
Histone Lysine Methyltransferase ◽  
Lysine Methyltransferase

Abstract The oncogenic fusion protein AML1-ETO retains the ability of AML1 to interact with the enhancer core DNA sequences, but blocks AML1-dependent transcription. Previous studies have shown that post-translational modification of AML1-ETO may play a role in its regulation. Here we report that AML1-ETO-positive patients, with high histone lysine methyltransferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. We find that EZH1 WD domain binds to the AML1-ETO NHR1 domain and methylates AML1-ETO at lysine 43 (Lys43). This requires the EZH1 SET domain, which augments AML1-ETO-dependent repression of tumor suppressor genes. Loss of Lys43 methylation by point mutation or domain deletion impairs AML1-ETO-repressive activity. These findings highlight the role of EZH1 in non-histone lysine methylation, indicating that cooperation between AML1-ETO and EZH1 and AML1-ETO site-specific lysine methylation promote AML1-ETO transcriptional repression in leukemia.

scholarly journals Loss of CRMP2 O-GlcNAcylation leads to reduced novel object recognition performance in mice

Open Biology ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 190192 ◽  
Author(s):  
Villo Muha ◽  
Ritchie Williamson ◽  
Rachel Hills ◽  
Alison D. McNeilly ◽  
Thomas G. McWilliams ◽  
...  
Keyword(s):  
Nervous System ◽  
Memory Impairment ◽  
Recognition Performance ◽  
Novel Object Recognition ◽  
Small Decrease ◽  
Post Translational Modification ◽  
Site Specific ◽  
Novel Object ◽  
Collapsin Response Mediator Protein ◽  
Mediator Protein

O-GlcNAcylation is an abundant post-translational modification in the nervous system, linked to both neurodevelopmental and neurodegenerative disease. However, the mechanistic links between these phenotypes and site-specific O-GlcNAcylation remain largely unexplored. Here, we show that Ser517 O-GlcNAcylation of the microtubule-binding protein Collapsin Response Mediator Protein-2 (CRMP2) increases with age. By generating and characterizing a Crmp2 S517A knock-in mouse model, we demonstrate that loss of O-GlcNAcylation leads to a small decrease in body weight and mild memory impairment, suggesting that Ser517 O-GlcNAcylation has a small but detectable impact on mouse physiology and cognitive function.

scholarly journals N- and O-Glycosylation Pathways in the Microalgae Polyphyletic Group

2020 ◽  
Vol 11 ◽  
Author(s):  
Elodie Mathieu-Rivet ◽  
Narimane Mati-Baouche ◽  
Marie-Laure Walet-Balieu ◽  
Patrice Lerouge ◽  
Muriel Bardor
Keyword(s):  
Recombinant Proteins ◽  
Metabolic Pathways ◽  
Phylogenetic Diversity ◽  
State Of The Art ◽  
Protein Glycosylation ◽  
Expression Systems ◽  
Post Translational Modification ◽  
Photosynthetic Organisms ◽  
Biological Features ◽  
Heterologous Expression Systems

The term microalga refers to various unicellular and photosynthetic organisms representing a polyphyletic group. It gathers numerous species, which can be found in cyanobacteria (i.e., Arthrospira) as well as in distinct eukaryotic groups, such as Chlorophytes (i.e., Chlamydomonas or Chlorella) and Heterokonts (i.e., diatoms). This phylogenetic diversity results in an extraordinary variety of metabolic pathways, offering large possibilities for the production of natural compounds like pigments or lipids that can explain the ever-growing interest of industrials for these organisms since the middle of the last century. More recently, several species have received particular attention as biofactories for the production of recombinant proteins. Indeed, microalgae are easy to grow, safe and cheap making them attractive alternatives as heterologous expression systems. In this last scope of applications, the glycosylation capacity of these organisms must be considered as this post-translational modification of proteins impacts their structural and biological features. Although these mechanisms are well known in various Eukaryotes like mammals, plants or insects, only a few studies have been undertaken for the investigation of the protein glycosylation in microalgae. Recently, significant progresses have been made especially regarding protein N-glycosylation, while O-glycosylation remain poorly known. This review aims at summarizing the recent data in order to assess the state-of-the art knowledge in glycosylation processing in microalgae.

Transduction-related cointegrate formation between staphylococcal plasmids: A new type of site-specific recombination

Plasmid ◽  
1981 ◽  
Vol 6 (2) ◽  
pp. 159-172 ◽  
Author(s):  
Richard P. Novick ◽  
Serban Iordanescu ◽  
Marietta Surdeanu ◽  
Irit Edelman
Keyword(s):  
Site Specific ◽  
Site Specific Recombination ◽  
New Type

scholarly journals Multiplex Genome Editing in Yeast by CRISPR/Cas9 – A Potent and Agile Tool to Reconstruct Complex Metabolic Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Joseph Christian Utomo ◽  
Connor Lorne Hodgins ◽  
Dae-Kyun Ro
Keyword(s):  
Genome Editing ◽  
Metabolic Pathways ◽  
Functional Characterization ◽  
Primary Metabolism ◽  
Biosynthetic Pathways ◽  
Post Translational Modification ◽  
Precise Integration ◽  
Specialized Metabolism ◽  
Specialized Metabolites ◽  
Plant Specialized Metabolism

Numerous important pharmaceuticals and nutraceuticals originate from plant specialized metabolites, most of which are synthesized via complex biosynthetic pathways. The elucidation of these pathways is critical for the applicable uses of these compounds. Although the rapid progress of the omics technology has revolutionized the identification of candidate genes involved in these pathways, the functional characterization of these genes remains a major bottleneck. Baker’s yeast (Saccharomyces cerevisiae) has been used as a microbial platform for characterizing newly discovered metabolic genes in plant specialized metabolism. Using yeast for the investigation of numerous plant enzymes is a streamlined process because of yeast’s efficient transformation, limited endogenous specialized metabolism, partially sharing its primary metabolism with plants, and its capability of post-translational modification. Despite these advantages, reconstructing complex plant biosynthetic pathways in yeast can be time intensive. Since its discovery, CRISPR/Cas9 has greatly stimulated metabolic engineering in yeast. Yeast is a popular system for genome editing due to its efficient homology-directed repair mechanism, which allows precise integration of heterologous genes into its genome. One practical use of CRISPR/Cas9 in yeast is multiplex genome editing aimed at reconstructing complex metabolic pathways. This system has the capability of integrating multiple genes of interest in a single transformation, simplifying the reconstruction of complex pathways. As plant specialized metabolites usually have complex multigene biosynthetic pathways, the multiplex CRISPR/Cas9 system in yeast is suited well for functional genomics research in plant specialized metabolism. Here, we review the most advanced methods to achieve efficient multiplex CRISPR/Cas9 editing in yeast. We will also discuss how this powerful tool has been applied to benefit the study of plant specialized metabolism.

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