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Table of Contents for this page:

  • Current Issue
  • Advanced Online Publications Articles

  • Current Issue of Nature Structural and Molecular Biology

    Nature Structural aamp; Molecular Biology - Issue - science feeds

  • An expanding universe of mRNA modifications

  • 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.

  • PARP1 and CBP lose their footing in cancer

  • 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.

  • DNA methylation: old dog, new tricks?

  • 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.

  • Cross-talking noncoding RNAs contribute to cell-specific neurodegeneration in SCA7

  • 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.

  • Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor

  • Structural and biochemical analyses of full-length human BRCA2 reveal how it facilitates RAD51-mediated homologous recombination to repair DNA double-strand breaks.

  • A genome-wide map of adeno-associated virus–mediated human gene targeting

  • 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 free and antagonist-bound states of humanα9 nicotinic receptor extracellular domain

  • Crystal structures of the extracellular domain of human nAChR, in its apo form and with antagonists methyllycaconitine orα-bungarotoxin bound, are presented. The structures provide insight into the channel-opening mechanism of nAChRs and their pharmacological properties.

  • MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation

  • 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.

  • Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport

  • 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.

  • Mechanisms for U2AF to define 3′ splice sites and regulate alternative splicing in the human genome

  • 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.

  • A mechanism for intracellular release of Na+ by neurotransmitter/sodium symporters

  • 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.

  • Crystal structure of the vitamin B3 transporter PnuC, a full-length SWEET homolog

  • 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.

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    Nature -Advance Online Publications

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    Nature Structural aamp; Molecular Biology - AOP - science feeds

  • Stapled HIV-1 peptides recapitulate antigenic structures and engage broadly neutralizing antibodies

  • Peptide hydrocarbon stapling is used to generate protease-resistant HIV-1 MPER antigens that mimic the conformation of viral epitopes and that are recognized by two different broadly neutralizing antibodies to HIV.

  • Structural basis for membrane targeting of the BBSome by ARL6

  • The BBSome is required for formation of primary cilia, sensory organelles whose dysfunction is linked to genetic disorders. Lorentzen and colleagues offer insight into BBSome membrane recruitment, providing a molecular rationale for common disease mutations.

  • Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit

  • 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.

  • Structural determinants of integrinβ-subunit specificity for latent TGF-β

  • Integrinα-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.

  • BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones

  • BRD4, a key target of the clinically relevant BET inhibitor JQ1, thought to function by releasing Pol II from promoter-proximal pausing, is shown to promote Pol II elongation by acting as a histone chaperone.

  • Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis by inhibiting the AKT pathway

  • 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.

  • Internal motions prime cIAP1 for rapid activation

  • 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.

  • Cryo-EM reveals different coronin binding modes for ADP– and ADP–BeFx actin filaments

  • 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.

  • Structural basis for interaction of a cotranslational chaperone with the eukaryotic ribosome

  • 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.

  • Structure of AMP-PNP–bound BtuCD and mechanism of ATP-powered vitamin B12 transport by BtuCD–F

  • A new crystal structure of BtuCD, a bacterial ABC transporter that uses ATP hydrolysis to drive vitamin B12 uptake, bound to an AMP-PNP nucleotide, completes the structural elucidation of intermediates in the transport cycle and reveals how ATP accelerates transport.

  • Local slowdown of translation by nonoptimal codons promotes nascent-chain recognition by SRP in vivo

  • Analyses of yeast codon usage and ribosome profiling data reveal a nonoptimal codon cluster in the mRNAs of ER-targeted proteins, downstream of the SRP-binding site, that would slow down translation to promote SRP interaction.
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