Nature Structural & Molecular Biology Contents: July 2013 Volume #20 pp 769-913

TABLE OF CONTENTS July 2013 Volume 20, Issue 7 News and Views Research Highlights Perspective Articles Resource Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement WE launched in 2011 YOU published 2000 papers with us OUR impact factor is 2.927* Discover what we can do together.   nature.com/scientificreports  *2012 Journal Citation Reports® (Thomson Reuters, 2013)     News and Views Top Activating silent Argonautes   pp769 - 771 Mary Anne Kidwell and Jennifer A Doudna doi:10.1038/nsmb.2620 Multiple Argonaute proteins are implicated in gene silencing by RNA interference (RNAi), but only one is known to be an endonuclease that can cleave target mRNAs. Chimeric Argonaute proteins now reveal an unexpected mechanism by which mutations distal to the catalytic center can unmask intrinsic catalytic activity, results hinting at structurally mediated regulation. See also: Article by Hauptmann et al. | Article by Schürmann et al. Antibodies expose multiple weaknesses in the glycan shield of HIV   pp771 - 772 Max Crispin and Thomas A Bowden doi:10.1038/nsmb.2627 A shield of glycans coats the viral-envelope proteins of HIV. Recent work shows how broadly neutralizing antibodies can recognize this shield despite structural variation in these 'self' carbohydrate structures. See also: Article by Kong et al. | Article by Pancera et al. EMI1, a three-in-one ubiquitylation inhibitor   pp773 - 774 Hiroyuki Yamano doi:10.1038/nsmb.2626 The anaphase-promoting complex/cyclosome (APC/C) is restricted by metazoan protein early mitotic inhibitor 1 (EMI1), a natural, potent inhibitor. New findings suggest that the multimodal inhibitory mechanisms of EMI1 control APC/C-dependent ubiquitylation. See also: Article by Frye et al. Research Highlights Bacterial glutathione import | Sensing KATastrophe | SAS, refined Structural & Molecular Biology JOBS of the week Postdoc in Molecular Biology and Cancer Research Washington State University College of Pharmacy Research Associate / Plant Molecular Biologist (M / F) KWS Services Deutschland GmbH PhD Studentship - Molecular simulation of bacterial membranes University of Southampton - Chemistry Professorship in Molecular Design and Synthesis University of Zurich Postdoctoral Position in Molecular Biology Roswell Park Cancer Institute(RPCI) More Science jobs from Perspective Top SIMIBI twins in protein targeting and localization   pp776 - 780 Gert Bange and Irmgard Sinning doi:10.1038/nsmb.2605 SIMIBI-type NTP-binding proteins are an ancient subfamily of nucleotide-binding proteins that comprises both dimeric ATPases and GTPases (SIMIBI 'twins'). This Perspective focuses on a subset of SIMIBI proteins with a defined function in protein targeting and localization, and aims to define common mechanistic principles and differences for these proteins. Articles Top Conformational switching of the 26S proteasome enables substrate degradation   pp781 - 788 Mary E Matyskiela, Gabriel C Lander and Andreas Martin doi:10.1038/nsmb.2616 The proteasome 19S particle processes ubiquitinated substrates, unfolds the polypeptides and translocates them to the 20S core particle. Now cryo-EM analyses of the yeast proteasome in the presence of substrate show the 19S in an active conformation, with the AAA+ ring forming a wider central channel aligned with the 20S pore and the essential deubiquitinase Rpn11 positioned right above it. Homeostatic control of Argonaute stability by microRNA availability   pp789 - 795 Peter Smibert, Jr-Shiuan Yang, Ghows Azzam, Ji-Long Liu and Eric C Lai doi:10.1038/nsmb.2606 Argonaute proteins are essential for miRNA function. Now a study in fly and mammalian systems shows that miRNA availability has an effect on the steady-state levels of Argonaute proteins. Argonaute is degraded by the ubiquitin-proteasome pathway, and increased miRNA levels lead to stabilization and accumulation of Argonaute. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120    pp796 - 803 Leopold Kong, Jeong Hyun Lee, Katie J Doores, Charles D Murin, Jean-Philippe Julien et al. doi:10.1038/nsmb.2594 Some broadly neutralizing antibodies to HIV-1 recognize glycan-dependent epitopes on gp120. Now X-ray crystallography and EM approaches, along with functional analyses, reveal how one particular antibody (PGT135) recognizes three glycan groups and can accommodate their conformational and chemical diversity. Structural basis for diverse N-glycan recognition by HIV-1–neutralizing V1–V2–directed antibody PG16   pp804 - 813 Marie Pancera, Syed Shahzad-ul-Hussan, Nicole A Doria-Rose, Jason S McLellan, Robert T Bailer et al. doi:10.1038/nsmb.2600 Some broadly neutralizing antibodies against HIV-1 recognize glycopeptide epitopes in the gp120 V1–V2 region. Now X-ray crystallography and NMR approaches, together with functional analyses of two such antibodies (PG9 and PG16), reveal how glycan binding specificity is achieved. The authors also created a chimeric Fab that showed improved neutralization activity. Turning catalytically inactive human Argonaute proteins into active slicer enzymes   pp814 - 817 Judith Hauptmann, Anne Dueck, Simone Harlander, Janina Pfaff, Rainer Merkl et al. doi:10.1038/nsmb.2577 Argonaute (Ago) proteins that cleave target RNAs are known as slicer enzymes. Extensive mutagenesis studies combined with in vitro cleavage assays and structural modeling have now enabled catalytically inactive human Ago1 and Ago3 to be turned into slicer enzymes, providing insight into the molecular basis of human Ago1 and Ago3 inactivity. See also: News and Views by Kidwell & Doudna Molecular dissection of human Argonaute proteins by DNA shuffling   pp818 - 826 Nina Schürmann, Leonardo G Trabuco, Christian Bender, Robert B Russell and Dirk Grimm doi:10.1038/nsmb.2607 What makes human Argonaute 2 (Ago2) slicing competent in contrast to AGO1, 3 and 4, which lack RNA cleavage activity, has remained unclear. Now, a molecular evolution approach, called DNA family shuffle (DFS), reveals features of AGO1, 3 and 4 that explain their RNA-slicing deficiency and suggests the juxtaposition and combined action of multiple disseminated protein modules. See also: News and Views by Kidwell & Doudna Electron microscopy structure of human APC/CCDH1–EMI1 reveals multimodal mechanism of E3 ligase shutdown   pp827 - 835 Jeremiah J Frye, Nicholas G Brown, Georg Petzold, Edmond R Watson, Christy R R Grace et al. doi:10.1038/nsmb.2593 APC/C is an E3 ligase complex of ~1.5 MDa that regulates cell division. APC/CCDH1 is inhibited during interphase by EMI1. Now, NMR spectroscopy, electron microscopy and enzymology analyses are integrated, revealing that EMI1's 143-residue C-terminal domain binds distinct regions of APC/CCDH1 to block the substrate-binding site and inhibit ubiquitin-chain elongation. See also: News and Views by Yamano Nucleosome dynamics regulates DNA processing   pp836 - 842 Nicholas L Adkins, Hengyao Niu, Patrick Sung, Craig L Peterson doi:10.1038/nsmb.2585 Double-strand-break repair by homologous recombination requires processing of the DNA ends by resection. In vitro and in vivo analysis of the Exo1 and Sgs1–Dna2 resection pathways in budding yeast demonstrates that both resection pathways are hindered by the presence of nucleosomes and require distinct chromatin remodeling events to navigate the chromatin structure. Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding   pp843 - 850 Arzu Sandikci, Felix Gloge, Michael Martinez, Matthias P Mayer, Rebecca Wade et al. doi:10.1038/nsmb.2615 Nascent polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting. Kinetic analyses now demonstrate that N-terminal processing enzymes have fast ribosome binding kinetics, and premature chaperone recruitment or folding negatively affects processing efficiency, thereby separating nascent chain processing from later events. Bimodal expression of PHO84 is modulated by early termination of antisense transcription   pp851 - 858 Manuele Castelnuovo, Samir Rahman, Elisa Guffanti, Valentina Infantino, Françoise Stutz et al. doi:10.1038/nsmb.2598 The presence of PHO84 sense and antisense transcripts in single cells is strongly anticorrelated, suggesting a switch-like regulation mechanism. Data from single-molecule fluorescent in situ hybridization experiments provide evidence that the exosome component Rrp6 does not degrade full-length PHO84 antisense transcripts but prevents antisense transcription elongation by favoring early termination. A ternary AppA–PpsR–DNA complex mediates light regulation of photosynthesis-related gene expression   pp859 - 867 Andreas Winkler, Udo Heintz, Robert Lindner, Jochen Reinstein, Robert L Shoeman et al. doi:10.1038/nsmb.2597 The repressor–antirepressor complex AppA–PpsR is a transcriptional regulator that permits Rhodobacter to switch between photosynthesis and respiration in response to light and oxygen. A combination of crystallography, hydrogen/deuterium-exchange MS and binding assays shows how illumination reduces the affinity of the complex for DNA and provides insight into the mechanism of signal transduction by photoreceptors. Molecular determinants of nucleosome retention at CpG-rich sequences in mouse spermatozoa   pp868 - 875 Serap Erkek, Mizue Hisano, Ching-Yeu Liang, Mark Gill, Rabih Murr et al. doi:10.1038/nsmb.2599 In mammalian spermatozoa, most of the genome is densely packaged by protamines, whereas only a very small percentage of nucleosomes is retained. Genome-wide nucleosome occupancy studies in mouse spermatozoa containing one percent residual histones now demonstrate that nucleosomes in sperm mainly localize to unmethylated CpG-rich sequences in a histone variant–specific manner and are differentially modified. The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals   pp876 - 883 Lisa C Watson, Kristopher M Kuchenbecker, Benjamin J Schiller, John D Gross, Miles A Pufall et al. doi:10.1038/nsmb.2595 Glucocorticoid receptor (GR) binds as a dimer to DNA, with the canonical binding sequence featuring two half-sites, each bound by one monomer, separated by a 3-bp spacer. The specific bases contacted by GR are known to direct receptor activity. Now NMR and functional analyses show that nonspecific interactions, including with the spacer region, can also affect GR conformation and activity. A bacterial-like mechanism for transcription termination by the Sen1p helicase in budding yeast   pp884 - 891 Odil Porrua and Domenico Libri doi:10.1038/nsmb.2592 The yeast Sen1p helicase is involved in the transcription termination of most noncoding RNAs transcribed by RNA polymerase II. In vitro analyses now show that Sen1p is the key enzyme in the termination reaction and reveal important features of the mechanism, which resembles that of bacterial termination factor Rho. Structural mimicry in transcription regulation of human RNA polymerase II by the DNA helicase RECQL5    pp892 - 899 Susanne A Kassube, Martin Jinek, Jie Fang, Susan Tsutakawa and Eva Nogales doi:10.1038/nsmb.2596 The RECQL5 DNA helicase interacts with RNA polymerase II (Pol II) and inhibits transcription through an unknown mechanism. A series of structural and functional analyses now reveals that RECQL5 sterically blocks elongation while also competing with elongation factor TFIIS for binding to Pol II, suggesting a dual mode of transcriptional repression. Allosteric opening of the polypeptide-binding site when an Hsp70 binds ATP    pp900 - 907 Ruifeng Qi, Evans Boateng Sarbeng, Qun Liu, Katherine Quynh Le, Xinping Xu et al. doi:10.1038/nsmb.2583 The 70-kDa heat-shock protein 70 (Hsp70) molecular chaperones have a nucleotide binding domain and a substrate binding domain that become allosterically coupled when Hsp70s bind ATP. The crystal structure of the prototypical Hsp70, Escherichia coli DnaK, in an ATP-bound state is now presented. The structure and functional analyses reveal the conformational changes and interdomain interactions that underlie allosteric coupling. Resource Top Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer   pp908 - 913 Zhou Du, Teng Fei, Roel G W Verhaak, Zhen Su, Yong Zhang et al. doi:10.1038/nsmb.2591 By integrating the expression profiles of long noncoding RNAs (lncRNAs) with clinical outcome and somatic copy-number alteration, the authors identified new lncRNAs that are associated with certain cancer subtypes and clinical prognoses. Experimental validation of the prostate cancer cell growth dependence of two new lncRNAs demonstrates the power of this approach for discovering disease-related lncRNAs. Top Advertisement Nature Publishing Index 2012 Global The Nature Publishing Index (NPI) ranks institutions and countries according to the number of primary research articles they publish in the Nature family of journals in a one-year period. 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