|Nature Structural aamp; Molecular Biology - Issue - nature.com science feeds|
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.
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.
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.
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.
Two new studies of the CRISPR nuclease Cpf1 reveal the structural and catalytic flexibility of this leaner, meaner alternative to Cas9.
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.
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 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.
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.
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.
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.
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.
The CARD-only protein INCA inhibits inflammasome assembly by capping caspase-1 CARD oligomers and preventing their further polymerization.
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.
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.
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.
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.
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.
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).
|Nature Structural aamp; Molecular Biology - AOP - nature.com science feeds|
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.