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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

  • α-synuclein folds: the cards are on the table

  • All current evidence indicates a central role forα-synuclein (α-SYN) amyloid fibrils in Parkinson's disease and other synucleinopathies, but the precise relationship between amyloid aggregates and the resulting phenotype remains poorly understood, partly because of the lack of reliable three-dimensional structures. In this issue, the structure of a toxic α-SYN fibril is now presented at unprecedented resolution.

  • SIRT6: a new guardian of mitosis

  • The sirtuin family protein SIRT6 is a stress-responsive NAD-dependent histone deacetylase with key roles in glucose homeostasis, DNA repair and cellular lifespan. SIRT6 is now shown to mediate deacetylation of histone H3 Lys18 specifically at pericentric chromatin, thus maintaining transcriptional silencing of satellite repeats in a manner independent of HP1 and trimethylated H3 Lys9, thereby assuring correct segregation of chromosomes.

  • Step back for seminal translation

  • Translation elongation entails a one-codon movement of the mRNA–tRNA complex along the mRNA and is catalyzed by the forward translocase EF-G. The structurally related back-translocase EF4 catalyzes movement in the opposite direction when the ribosome stalls, but its physiological role in mammals had been unknown. Genetic ablation of EF4 in mice is now found to cause testis-specific mitochondrial deficiency and impaired spermatogenesis.

  • A novel regulatory mechanism for the brown-fat uncoupling protein?

  • Brown fat has a tremendous capacity to oxidize fatty acids and generate heat, owing to the presence of an 'uncoupling protein', UCP1. The fatty acids themselves are understood to activate UCP1, but Chouchani et al. now propose that oxidation of a critical cysteine residue on UCP1 is additionally required to sensitize the protein to fatty acids.

  • Cpf1 shape-shifts for streamlined CRISPR cleavage

  • Two new studies of the CRISPR nuclease Cpf1 reveal the structural and catalytic flexibility of this leaner, meaner alternative to Cas9.

  • Translocation: lights, camera, and action

  • The fundamental mechanics of how EF-G catalyzes translocation of the mRNA and tRNA pairs on the ribosome has been intensely studied for over three decades. Two kinetic studies now reveal the sequence of events and the timing of key conformational changes in the ribosome during translocation and identify new intermediates in this complex process.

  • Regulating the construction and demolition of the synaptonemal complex

  • The synaptonemal complex (SC) connects homologous chromosomes in meiotic prophase, thus promoting genetic exchange and ensuring accurate chromosomal segregation at anaphase. In this Review, the authors discuss the structural organization of the SC and how its assembly, maintenance and disassembly are regulated in yeast and metazoans.The synaptonemal complex (SC) connects homologous chromosomes in meiotic prophase, thus promoting genetic exchange and ensuring accurate chromosomal segregation at anaphase. In this Review, the authors discuss the structural organization of the SC and how its assembly, maintenance and disassembly are regulated in yeast and metazoans.

  • Structural basis for therapeutic inhibition of complement C5

  • Structural and functional analyses of a new family of tick-derived C5 inhibitors in complex with inhibitor OmCI and therapeutic antibody eculizumab reveal diverse mechanisms for inhibition and provide insight into C5 activation by C5 convertases.

  • BTG4 is a meiotic cell cycle–coupled maternal-zygotic-transition licensing factor in oocytes

  • B-cell translocation gene-4 (Btg4) bridges interactions of translation initiation factor eIF4E and CCR4–NOT deadenylase, thus triggering decay of maternal mRNA during mouse oocyte maturation.

  • Structural basis for specific inhibition of Autotaxin by a DNA aptamer

  • SELEX selections and crystallographic analyses have allowed development of a DNA aptamer that inhibits autotaxin with high potency and specificity, and exhibits efficacy against bleomycin-induced pulmonary fibrosis in model mice.

  • Resolving individual steps of Okazaki-fragment maturation at a millisecond timescale

  • High-resolution kinetic analysis and enzyme trapping assays reveal how PCNA coordinates 5′-flap generation and processing by Pol δ and FEN1 during Okazaki-fragment maturation.

  • Solid-state NMR structure of a pathogenic fibril of full-length humanα-synuclein

  • α-synuclein amyloid fibrils are associated with Parkinson's disease. SSNMR analyses now reveal the atomic structure of a pathogenic human α-synuclein fibril, providing a framework for understanding fibril nucleation, propagation and interactions with small molecules.

  • Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism

  • The CARD-only protein INCA inhibits inflammasome assembly by capping caspase-1 CARD oligomers and preventing their further polymerization.

  • Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity

  • Crystal structures of the human ADAR2 deaminase domain in complex with RNA duplexes reveal the mechanisms for ADAR2's action and explain its substrate preference. The work also provides a rationale to understand disease-related mutations.

  • SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence

  • The sirtuin family protein SIRT6 maintains pericentric heterochromatin silencing at human centromeres through deacetylation of a newly discovered substrate, H3K18, thus protecting cells against mitotic errors, genomic instability and cellular senescence.

  • Mammalian elongation factor 4 regulates mitochondrial translation essential for spermatogenesis

  • Genetic ablation of EF4 in mice leads to male sterility due to mitochondrial translation defects, which can be compensated for in somatic tissues by mTOR-mediated upregulation of cytoplasmic translation.

  • Expansion of antisense lncRNA transcriptomes in budding yeast species since the loss of RNAi

  • RNA interference constrains antisense lncRNA transcriptomes, and its loss during budding yeast evolution is associated with an increase in genome-wide expression of antisense lncRNAs.

  • Zika virus NS1 structure reveals diversity of electrostatic surfaces among flaviviruses

  • The crystal structure of the C-terminal region of Zika virus nonstructural protein 1 (NS1) reveals a fold similar to those of other flaviviruses (dengue and West Nile viruses) but different surface electrostatic features.

  • Universality of supersaturation in protein-fiber formation

  • An analysis of previously published data on fiber formation by sickle-cell hemoglobin reveals a universal curve when delay time is plotted against supersaturation (ratio of protein concentration to solubility).

  • Corrigendum: Structure of a prokaryotic fumarate transporter reveals the architecture of the SLC26 family

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    Nature -Advance Online Publications

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    Nature Structural aamp; Molecular Biology - AOP - science feeds

  • Functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation

  • MSL1, a component of the Drosophila dosage compensation complex, genetically and biochemically interacts with CDK7, a subunit of the TFIIH transcription factor, thus revealing a complex interplay between MSL1 and the general transcriptional machinery.

  • Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger

  • A series of crystal structures and calculated free-energy landscapes of a Na+/Ca2+ exchanger explain how its alternating-access mechanism is controlled by the ion occupancy, thus leading to coupled antiport.

  • Structure of the Dcp2–Dcp1 mRNA-decapping complex in the activated conformation

  • Crystal structures, along with biochemistry data, capture the active form of the Dcp2 decapping enzyme in complex with Dcp1 and a peptide from Edc1, thus revealing the mechanism of activation by Dcp1 and Edc1 activators.

  • BRD4 is a histone acetyltransferase that evicts nucleosomes from chromatin

  • In vitro and in vivo analyses show that BRD4 has intrinsic acetyltransferase activity targeting histones H3 and H4, and BRD4 acetylation of H3 K122 results in histone eviction, nucleosome clearance and chromatin decompaction.

  • Lactase nonpersistence is directed by DNA-variation-dependent epigenetic aging

  • Age-dependent epigenetic changes that are influenced by genetic factors contribute to lactase nonpersistence, which is linked to the inability of adult mammals to digest lactose.

  • Allosteric inhibition of antiapoptotic MCL-1

  • Identification of an allosteric mechanism disrupting the antiapoptotic BH3 binding activity of MCL-1 offers a new approach for targeting the apoptotic resistance of human cancers.

  • Structure of a group II intron in complex with its reverse transcriptase

  • A 3.8-Å cryo-EM structure of a bacterial group IIA intron in complex with its intron-encoded protein reveals how the reverse transcriptase domain interacts with the mobile intron RNA as well as structural similarities with eukaryotic telomerase and spliceosomal components.

  • Crystal structures of a group II intron maturase reveal a missing link in spliceosome evolution

  • Crystal structures of the reverse transcriptase domains of two group II intron–encoded proteins reveal their similarity to the RT domain of splicing factor Prp8, thus suggesting a common ancestry shared by group II introns and the spliceosome.

  • Crystal structure of the prefusion surface glycoprotein of the prototypic arenavirus LCMV

  • The crystal structure of the GP1–GP2 complex of the prototypical arenavirus LCMV in prefusion form sheds light on the conformational changes that the arenavirus glycoprotein undergoes to cause fusion.

  • Extensive subunit contacts underpin herpesvirus capsid stability and interior-to-exterior allostery

  • Capsids from two herpesviruses (HSV-1 and PRV), imaged inside intact virions, are analyzed by cryo-EM. The maps allowed the construction of a complete model of subunit and domain organization, revealing extensive subunit contacts.

  • Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer

  • New data reveal that LINP1, a lncRNA overexpressed in triple-negative breast cancer, interacts with the Ku70–Ku80 complex and DNA-PKcs, thereby promoting NHEJ-mediated DNA double-strand-break repair.

  • Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking

  • Analysis of changes in the EGFR interactome, ubiquitinome, phosphoproteome and proteome in response to EGF or TGF-α identifies RAB7 phosphorylation and RCP recruitment to EGFR as ligand-specific switches controlling receptor trafficking, signal duration and cellular responses.
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