Lysine
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Quantitative profiling of JMJD6-catalysed lysine hydroxylation reveals residue-dependent oxygen sensitivity
Lysine hydroxylation is increasingly recognised as a widespread post-translational modification in human cells, with more than 100 modified sites identified to date. Jumonji domain-containing protein 6 (JMJD6) catalyses hydroxylation at multiple lysines within lysine-rich regions and is a major contributor to this modification across the proteome. As JMJD6 requires oxygen as a co-substrate, lysine hydroxylation has been proposed to couple oxygen availability to cellular function.
Molecular Basis of Histone H3 Reading and Writing by Legionella pneumophila SET Domain Lysine Methyltransferases
RomA and its highly conserved strain ortholog LegAS4 are SET and ankyrin domain-containing effector proteins of the intracellular bacterial pathogen Legionella pneumophila. These enzymes are secreted into host cells, where they translocate to the nucleus and methylate Lys14 in histone H3 (H3K14), a novel post-translation modification (PTM) that reprograms gene expression and promotes bacterial replication. To elucidate their H3K14 substrate specificity, we determined the crystal structures...
Overexpression of Eaf1, a subunit of the NuA4 lysine acetyl transferase complex, rescues growth defects in the budding yeast H3K36M oncohistone model via histone H4 tail acetylation
Histone proteins are critical for regulating functions that occur at DNA, such as gene expression. Certain mutations in histone genes were characterized to drive oncogenesis, termed oncohistones, and one of the first identified oncohistones is H3K36M. While humans have a high copy number of H3 genes, making genetic engineering in cell lines challenging, budding yeast only have two H3 genes. Additionally, histone H3 shares 90% sequence identity between budding yeast and humans, making it a...
Histone succinylation directly inhibits Jumonji domain demethylases and stabilizes repressive chromatin states
Herein we uncover a relationship between histone succinylation and Jumonji (JmjC) domain-containing histone demethylases. We used quantitative proteomics and peptide pull-down assays to identify JmjC demethylases as candidate interactors with succinylated histone peptides. Succinyl-lysine peptides bind and inhibit the catalytic activity of JmjC demethylases in a dose-dependent manner.
SIRT7 regulates dosage compensation and safeguards the female X chromosome
Abstract Sirtuins are deacetylases implicated in stress responses and longevity in mammals1,2. Although their differential impact on disease for the two sexes has been noted3,4,5,6,7, the underlying reasons are unclear. Here, using Sirt7 as a model in mice, we examine the mechanisms leading to sex differences and find that Sirt7−/− female mice have decreased fitness throughout their lifespan.
Structure-Aware Prediction of PROTAC-Mediated Protein Degradability via Graph Neural Networks
Announce Type: cross Abstract: Proteolysis-targeting chimeras (PROTACs) can selectively degrade disease-causing proteins, yet predicting which targets are amenable to degradation remains a critical bottleneck: existing computational methods require the complete PROTAC molecular structure, information unavailable before synthesis. We present DegradoMap, a graph neural network that predicts PROTAC-mediated degradability from protein structure and E3 ligase identity alone -- the minimal...
The advertising cartel coming to your web browser
The advertising cartel coming to your web browser When Meta, Google and Apple agree on a “privacy” feature, watch out. The three companies (along with Mozilla, which is on one of their “ad features in the browser” kicks again) are drawing up a built-in advertising measurement system, called Attribution Level 1, as a standard feature of web browsers. The system is intended to measure the effectiveness of advertising by enabling advertisers to correlate “impressions,” the occasions on which...