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Reconstitution of a 15-subunit functional human Mediator complex establishes direct physical and functional interactions of key MED subunits with both Pol II and TFIID to support transcriptional activation and identifies subunits critical for module association and assembly.
Proapoptotic signals trigger the transition of cIAP1 from an autoinhibited monomeric form to an activated dimer. NMR and time-resolved SAXS analyses reveal the conformational dynamics of the cIAP1 monomer that facilitates rapid and irreversible activation.
Integrin α-β heterodimers recognize ligands with RGD peptide motifs, but how they differentiate between the numerous RGD-containing proteins is unknown. Here, Springer and colleagues elucidate the structural basis for ligand binding specificity of the integrin β subunit.
Work in Caenorhabditis elegans identifies a substrate for CED-3 caspase during apoptosis, CNT-1. The cleavage product of CNT-1 localizes to the plasma membrane and blocks the activation of AKT by PIP3, suppressing AKT's prosurvival effects.
The fate of an mRNA is regulated by internal base modifications that generate the modified nucleotides N6-methyladenosine, 5-methylcytosine and inosine. Three new studies show that yeast and human mRNAs also contain pseudouridine residues and that pseudouridylation is induced in various stress states, hinting at a new pathway for post-transcriptional control of mRNA.
The human histone macroH2A.1.1 recruits activated PARP1 enzyme to chromatin through its poly(ADP-ribose)-binding macrodomain. New work shows that PARP1 and CBP can be displaced from chromatin in cancer cells that have lost macroH2A.1.1, thus leading to changes in histone H2B acetylation at cancer-relevant genes.
Emerging evidence from genome-wide analyses reveals that DNA methylation, an epigenetic modification associated with the repression of gene expression, can also promote transcriptional activation.
Cryo-EM structures of the co-translational chaperone RAC in association with the ribosome suggest that RAC regulates protein translation by mechanically coupling cotranslational folding with the peptide-elongation cycle.
Cryo-EM analyses of coronin in complex with F-actin in its ADP-bound or ADP–BeFx–bound state and fitting of atomic models explain the nucleotide-dependent effects of coronin on cofilin-assisted remodeling of F-actin.
The X-ray crystal structure of ScaDMT, a bacterial member of the solute carrier 11 transporter family, identifies conserved residues within the substrate-binding site that confer metal-ion selectivity.
U2AF is known to affect 3′-splice-site selection. Here, Fu and colleagues use genome-wide analysis of U2AF-RNA interactions to define U2AF's key roles in gene expression and regulated splicing in normal and disease states.
CAG-repeat expansion in the housekeeping gene ATXN7 causes the neurodegenerative disorder SCA7. Now ATXN7 protein is found to promote transcription and expression of miR-124, which in turn mediates cross-talk between lnc-SCA7 and ATXN7 transcripts.
Histone variant macroH2A1 represses gene expression in heterochromatin. New data show that it can also stimulate transcription by cooperating with PARP-1 to promote CBP-mediated H2B acetylation and that this regulatory function is lost in cancer cells.
Yeast cells display synchronized oscillation between phases of high and low oxygen consumption accompanied by a program of cyclical gene expression. A study monitoring mRNA levels, histone modifications and chromatin occupancy of histone modifiers during the yeast metabolic cycle (YMC) at high temporal resolution reveals both 'just-in-time' supply of YMC gene products and new patterns of chromatin reconfiguration associated with transcriptional regulation.
An X-ray crystal structure of substrate-bound Neisseria PnuC, a bacterial member of the SWEET family of transporters, provides key insights into the translocation mechanism and potential evolution of these membrane proteins.
We report the outcomes of the discussion initiated at the workshop entitled A 3D Cellular Context for the Macromolecular World and propose how data from emerging three-dimensional (3D) cellular imaging techniques—such as electron tomography, 3D scanning electron microscopy and soft X-ray tomography—should be archived, curated, validated and disseminated, to enable their interpretation and reuse by the biomedical community.
Structural and biochemical analyses of full-length human BRCA2 reveal how it facilitates RAD51-mediated homologous recombination to repair DNA double-strand breaks.
Crystal structures of MhsT, a bacterial member of the neurotransmitter/sodium symporter family, in an occluded, inward-facing state with bound sodium and substrate reveal conformational changes during the transport cycle that provide new insights into the mechanism of cytoplasmic sodium release.
A genome-wide screen of gene targeting by an adeno-associated virus vector in human cells reveals that target sites are preferentially located where transcription occurs in the opposite direction from DNA replication, suggesting that colliding polymerases promote homologous recombination.
Crystal structures of the extracellular domain of human nAChR, in its apo form and with antagonists methyllycaconitine or α-bungarotoxin bound, are presented. The structures provide insight into the channel-opening mechanism of nAChRs and their pharmacological properties.
