eLife
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A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotesThe advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged be... ... hiện toàn bộ
eLife - Tập 5
Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activationT cell expansion and differentiation are critically dependent on the transcription factor c-Myc (Myc). Herein we use quantitative mass-spectrometry to reveal how Myc controls antigen receptor driven cell growth and proteome restructuring in murine T cells. Analysis of copy numbers per cell of >7000 proteins provides new understanding of the selective role of Myc in controlling the prote... ... hiện toàn bộ
eLife - Tập 9
Common activation mechanism of class A GPCRsClass A G-protein-coupled receptors (GPCRs) influence virtually every aspect of human physiology. Understanding receptor activation mechanism is critical for discovering novel therapeutics since about one-third of all marketed drugs target members of this family. GPCR activation is an allosteric process that couples agonist binding to G-protein recruitment, with the hallmark outward moveme... ... hiện toàn bộ
eLife - Tập 8
Membrane transporter dimerization driven by differential lipid solvation energetics of dissociated and associated statesOver two-thirds of integral membrane proteins of known structure assemble into oligomers. Yet, the forces that drive the association of these proteins remain to be delineated, as the lipid bilayer is a solvent environment that is both structurally and chemically complex. In this study, we reveal how the lipid solvent defines the dimerization equilibrium of the CLC-ec1 Cl-... hiện toàn bộ
eLife - Tập 10
NG2 glial cells integrate synaptic input in global and dendritic calcium signalsSynaptic signaling to NG2-expressing oligodendrocyte precursor cells (NG2 cells) could be key to rendering myelination of axons dependent on neuronal activity, but it has remained unclear whether NG2 glial cells integrate and respond to synaptic input. Here we show that NG2 cells perform linear integration of glutamatergic synaptic inputs and respond with increasing dendritic calcium eleva... ... hiện toàn bộ
eLife - Tập 5
Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicingRBM15, an RNA binding protein, determines cell-fate specification of many tissues including blood. We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578, leading to its degradation via ubiquitylation by an E3 ligase (CNOT4). Overexpression of PRMT1 in acute megakaryocytic leukemia cell lines blocks megakaryocyte terminal differentiation by ... ... hiện toàn bộ
eLife - Tập 4
Multiple knockout mouse models reveal lincRNAs are required for life and brain developmentMany studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of lncRNAs in various physiological conditions, we have developed a collection of 18 lncRNA knockout strains in which the locus is maintained transcriptionally active. Initial charac... ... hiện toàn bộ
eLife - Tập 2
Beam-induced motion correction for sub-megadalton cryo-EM particlesIn electron cryo-microscopy (cryo-EM), the electron beam that is used for imaging also causes the sample to move. This motion blurs the images and limits the resolution attainable by single-particle analysis. In a previous Research article (<xref ref-type="bibr" rid="bib3">Bai et al., 2013</xref>) we showed that correcting for this motion by processing movies from fast direct-e... ... hiện toàn bộ
eLife - Tập 3
Measuring the optimal exposure for single particle cryo-EM using a 2.6 Å reconstruction of rotavirus VP6Biological specimens suffer radiation damage when imaged in an electron microscope, ultimately limiting the attainable resolution. At a given resolution, an optimal exposure can be defined that maximizes the signal-to-noise ratio in the image. Using a 2.6 Å resolution single particle cryo-EM reconstruction of rotavirus VP6, determined from movies recorded with a total exposure of 100 elect... ... hiện toàn bộ
eLife - Tập 4
A platform for brain-wide imaging and reconstruction of individual neuronsThe structure of axonal arbors controls how signals from individual neurons are routed within the mammalian brain. However, the arbors of very few long-range projection neurons have been reconstructed in their entirety, as axons with diameters as small as 100 nm arborize in target regions dispersed over many millimeters of tissue. We introduce a platform for high-resolution, three-dimensio... ... hiện toàn bộ
eLife - Tập 5
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