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TABLE OF CONTENTS
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November 2013 Volume 20, Issue 11 |
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Research Highlights
Articles
Brief Communication
Technical Report
Resources
Addendum
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News and Views | Top |
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Articles | Top |
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Divergent evolution of protein conformational dynamics in dihydrofolate reductase pp1243 - 1249 Gira Bhabha, Damian C Ekiert, Madeleine Jennewein, Christian M Zmasek, Lisa M Tuttle et al. doi:10.1038/nsmb.2676 Analysis of primary protein sequences and tertiary structures has yielded important insights into the evolution of protein function, but little is known about the evolution of functional mechanisms and protein dynamics. An integrated approach including structural biology, mutagenesis, bioinformatics analyses and cell biology has now uncovered evolutionary aspects of the motions present in the dihydrofolate reductase enzyme family.
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Promiscuous RNA binding by Polycomb repressive complex 2 pp1250 - 1257 Chen Davidovich, Leon Zheng, Karen J Goodrich and Thomas R Cech doi:10.1038/nsmb.2679 Polycomb repressive complex 2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer, and it can be recruited to chromatin by long noncoding RNAs. In vitro binding studies and comparative analysis of genome-wide in vivo data now suggest a model for the maintenance of the repressed chromatin state by PRC2, directed by PRC2's promiscuous binding to nascent RNA transcripts.
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PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells pp1258 - 1264 Syuzo Kaneko, Jinsook Son, Steven S Shen, Danny Reinberg and Roberto Bonasio doi:10.1038/nsmb.2700 Polycomb repressive complex 2 (PRC2) acts as an epigenetic repressor by depositing repressive H3K27me3 marks, but how it is regulated and directed to specific genes remains unknown. PRC2 is now found to bind at low levels to many gene promoters, including active ones devoid of H3K27me3, and the EZH2 catalytic subunit binds directly to nascent transcripts.
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Conformation and dynamics of the periplasmic membrane-protein–chaperone complexes OmpX–Skp and tOmpA–Skp pp1265 - 1272 Björn M Burmann, Congwei Wang and Sebastian Hiller doi:10.1038/nsmb.2677 Skp is a bacterial chaperone that prevents aggregation of outer membrane proteins as they traverse the periplasmic space. The conformation and dynamics of Skp in complex with two OMPs are now examined by NMR spectroscopy. The analyses reveal that Skp provides a scaffold for its substrates, which in turn populate a dynamic conformational ensemble.
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A bacterial toxin catalyzing tyrosine glycosylation of Rho and deamidation of Gq and Gi proteins pp1273 - 1280 Thomas Jank, Xenia Bogdanovic, Christophe Wirth, Erik Haaf, Michael Spoerner et al. doi:10.1038/nsmb.2688 A new bacterial toxin from pathogen Photorhabdus asymbiotica is now described. The toxin contains a domain with glycosyltransferase activity that modifies a tyrosine residue of Rho GTPases in the host cell, inhibiting Rho activation and interaction with downstream effectors. The second domain is a glutamine deamidase that blocks GTP hydrolysis by Gaq/11 and Gai proteins.
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Structure and RNA-binding properties of the Not1–Not2–Not5 module of the yeast Ccr4–Not complex pp1281 - 1288 Varun Bhaskar, Vladimir Roudko, Jérôme Basquin, Kundan Sharma, Henning Urlaub et al. doi:10.1038/nsmb.2686 The Ccr4–Not complex is involved in several aspects of gene expression, including mRNA decay, translational repression and transcription. Structural, biochemical and functional analyses of the Not module, comprising the C-terminal regions of Not1, Not2 and Not5, suggest that it forms a platform for protein and nucleic acid interactions that are important for Ccr4–Not's many functions.
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Structure and assembly of the NOT module of the human CCR4–NOT complex pp1289 - 1297 Andreas Boland, Ying Chen, Tobias Raisch, Stefanie Jonas, Duygu Kuzuoglu-Öztürk et al. doi:10.1038/nsmb.2681 The CCR4–NOT deadenylase complex has a crucial role in post-transcriptional mRNA regulation, catalyzing the removal of mRNA poly(A) tails and consequently repressing translation and promoting mRNA degradation. The crystal structure of the human NOT module, formed by the CNOT1, CNOT2 and CNOT3 C-terminal regions, now provides a structural framework for understanding its assembly and functions.
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Structure of human mitochondrial RNA polymerase elongation complex pp1298 - 1303 Kathrin Schwinghammer, Alan C M Cheung, Yaroslav I Morozov, Karen Agaronyan, Dmitry Temiakov et al. doi:10.1038/nsmb.2683 Mitochondrial DNA is transcribed by a single-subunit RNA polymerase (mtRNAP) that is distantly related to the RNAP of bacteriophage T7. Together with biochemical data, the crystal structure of the mtRNAP elongation complex with DNA template and RNA transcript elucidates the elongation mechanism of mtRNAP and reveals striking differences as compared with the T7 transcription system.
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Mechanism of allosteric activation of SAMHD1 by dGTP pp1304 - 1309 Xiaoyun Ji, Ying Wu, Junpeng Yan, Jennifer Mehrens, Haitao Yang et al. doi:10.1038/nsmb.2692 The dNTPase SAMHD1 inhibits infection by HIV-1 and other retroviruses. In the presence of dGTP, the enzyme forms tetramers and becomes active, a process that is now elucidated by structural, biochemical and cellular analyses of human SAMHD1. Binding of dGTP to four allosteric sites promotes tetramerization and induces a conformational change in the substrate-binding pocket to activate the enzyme.
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Structural insights into H+-coupled multidrug extrusion by a MATE transporter pp1310 - 1317 Min Lu, Martha Radchenko, Jindrich Symersky, Rongxin Nie and Yi Guo doi:10.1038/nsmb.2687 Bacterial multidrug efflux transporters (MATEs) couple drug export to Na+ or H+ influx. A new crystal structure of the H+-coupled DinF transporter from Bacillus halodurans reveals differences in the substrate-binding sites and transport mechanisms of DinF and NorM MATE homologs.
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Brief Communication | Top |
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The structural basis of autotransporter translocation by TamA pp1318 - 1320 Fabian Gruss, Franziska Zähringer, Roman P Jakob, Björn M Burmann, Sebastian Hiller et al. doi:10.1038/nsmb.2689 The outer-membrane protein TamA is involved in autotransporter biogenesis in Escherichia coli. The crystal structure of TamA, determined to 2.3 Å, reveals a 16-strand β-barrel that is closed by a lid on its extracellular face. A weakened lateral wall in the barrel suggests the presence of a gate for substrate exit to the lipid bilayer.
See also: News and Views by van den Berg
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Technical Report | Top |
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Live visualization of chromatin dynamics with fluorescent TALEs pp1321 - 1324 Yusuke Miyanari, Céline Ziegler-Birling and Maria-Elena Torres-Padilla doi:10.1038/nsmb.2680 It has been challenging to label endogenous genomic sequences in living cells, and this has limited attempts to study the dynamics of nuclear architecture in genome function. In a newly developed methodology, transcription activator–like effectors (TALEs) were used to label endogenous repetitive genomic sequences to visualize nuclear positioning and chromatin dynamics in cultured mouse cells and embryos.
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Resources | Top |
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Analysis of microRNA-target interactions across diverse cancer types OPEN pp1325 - 1332 Anders Jacobsen, Joachim Silber, Girish Harinath, Jason T Huse, Nikolaus Schultz et al. doi:10.1038/nsmb.2678 Analysis of data from The Cancer Genome Atlas generates a pan-cancer network of 143 recurrent miRNA-target relationships. The identified miRNAs were frequently regulated by genetic and epigenetic alterations in cancer. The work also reveals that some miRNAs might coordinately regulate cancer pathways, such as miR-29 regulation of TET1 and TDG mRNAs, encoding components from the active DNA demethylation pathway.
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Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in Drosophila pp1333 - 1339 Georges St Laurent, Michael R Tackett, Sergey Nechkin, Dmitry Shtokalo, Denis Antonets et al. doi:10.1038/nsmb.2675 The accurate and thorough genome-wide detection of A-to-I editing has proven technically challenging. Using a combination of computational prediction and experimental validation, the authors report ~3,500 high-probability editing sites with sufficient accuracy to reveal the global patterns underlying biological functions of RNA editing in adult male Drosophila melanogaster.
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Addendum | Top |
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Noncoding RNAs prevent spreading of a repressive histone mark p1340 Claudia Keller, Raghavendran Kulasegaran-Shylini, Yukiko Shimada, Hans-Rudolf Hotz and Marc Bühler doi:10.1038/nsmb1113-1340
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Nature Collections TCGA pan-cancer analysis
The Cancer Genome Atlas Pan-cancer initiative examines the similarities and differences among the genomic and cellular alterations found in the first dozen tumor types to be profiled by TCGA. This first look across cancer offers new tools in genomics and bioinformatics and the prospect of repurposing targeted therapies directed by the molecular pathology of the tumors in addition to their clinical classification. Access the Collection and accompanying Podcast, FREE at: www.nature.com/tcga
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