Nature Structural & Molecular Biology Contents: January 2013 Volume #20 pp 1 - 133

TABLE OF CONTENTS January 2013 Volume 20, Issue 1 Meeting Report News and Views Research Highlights Review Articles Analysis Resource Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement We've got something to share with you Access the latest scientific news and research when and where you want it. Download the latest issues to browse at your convenience, zoom in on figures and images, save your searches and synchronize your bookmarks across devices. Tap in to find out more   Meeting Report Top A global view of Hsp90 functions   pp1 - 4 Gabriela Chiosis, Chad A Dickey and Jill L Johnson doi:10.1038/nsmb.2481 The Sixth International Conference on Hsp90 in 2012 revealed new functions of this key molecular chaperone. Attendees of the meeting at Les Diablerets, Switzerland, addressed new discoveries about Hsp90 and its cochaperones. News and Views Top Releasing the brakes on a chromatin-remodeling enzyme   pp5 - 7 Benjamin J. Manning and Craig L. Peterson doi:10.1038/nsmb.2482 Chromatin-remodeling enzymes use the energy from ATP hydrolysis to mobilize, disrupt or change the histone composition of nucleosomes, facilitating nearly every nuclear event. Two recent studies indicate that remodeling enzymes harness the power of an ancient constitutively active DNA translocase and that different remodeling enzymes may use specialized coupling domains that communicate the presence of nucleosomal epitopes to regulate translocase and remodeling activity. See also: Article by Mueller-Planitz et al. Sibling rivalry: competition between MHC class II family members inhibits immunity   pp7 - 10 Lisa K. Denzin and Peter Cresswell doi:10.1038/nsmb.2484 Peptide loading of major histocompatibility complex (MHC) class II molecules in the endosomes and lysosomes of antigen-presenting cells is catalyzed by human leukocyte antigen-DM (HLA-DM) and modulated by HLA-DO. In a structural study in this issue, Guce et al. show that HLA-DO is an MHC class II mimic and functions as a competitive and essentially irreversible inhibitor of HLA-DM activity, thereby inhibiting MHC class II antigen presentation. See also: Article by Guce et al. A popular engagement at the ends   pp10 - 12 Neal F. Lue, Eun Young Yu and Ming Lei doi:10.1038/nsmb.2483 Three recent studies converged on a specific protein-protein interface between TPP1 and telomerase as being crucial for the regulation of both telomerase recruitment and processivity in mammalian cells. An equivalent interaction appears to exist in budding yeast, making this a nearly universal means of telomerase regulation. Research Highlights Conformational selection | Protective degradation | Hybrid signals for BRCA1 Structural & Molecular Biology JOBS of the week Community Manager The Node / Development The Company of Biologists Ltd NERC PhD Studentship: Marine energy, fish and fisheries - conflict or coexistence? University of Exeter Informatics Manager University of Dundee, College of Life Sciences Postdoc studies on diabetes and beta-cell regeneration mice Karolinska Institute, Department for Cell and Molecular Biology More Science jobs from Structural & Molecular Biology EVENT 10th International Conference on Damage Assessment of Structures (DAMAS 2013) 08.-10.07.13 Dublin, Ireland More science events from Review Top Histone chaperones in nucleosome assembly and human disease   pp14 - 22 Rebecca J Burgess and Zhiguo Zhang doi:10.1038/nsmb.2461 Nucleosome assembly is crucial for the maintenance of genome stability and epigenetic information and is aided by histone chaperones. This Review discusses recent insights into the mechanisms and roles of histone chaperones in regulating nucleosome assembly and how alterations in nucleosome-assembly factors may be implicated in human diseases. Articles Top Structural characterization of a eukaryotic chaperone—the ribosome-associated complex   pp23 - 28 Christoph Leidig, Gert Bange, Jürgen Kopp, Stefan Amlacher, Ajay Aravind, Stephan Wickles, Gregor Witte, Ed Hurt, Roland Beckmann and Irmgard Sinning doi:10.1038/nsmb.2447 The eukaryotic ribosome-associated complex (RAC) chaperone is poorly understood. Structural analyses now provide insight into the catalytic inactivity and possible functions of the Ssz1 subunit and reveal that RAC interacts with the ribosome via the Zuo1 subunit. RAC crouches over the ribosomal exit tunnel, where its conformation may be controlled by the ribosomal expansion segment ES27. Structural plasticity of histones H3–H4 facilitates their allosteric exchange between RbAp48 and ASF1    pp29 - 35 Wei Zhang, Marek Tyl, Richard Ward, Frank Sobott, Joseph Maman, Andal S Murthy, Aleksandra A Watson, Oleg Fedorov, Andrew Bowman, Tom Owen-Hughes, Hassane El Mkami, Natalia V Murzina, David G Norman and Ernest D Laue doi:10.1038/nsmb.2446 Histone chaperone RbAp48 interacts with histones H3-H4 and delivers them to a second histone chaperone, ASF1, to be assembled into new nucleosomes. These interactions are now investigated, revealing that RbAp48 binds H3-H4 heterodimers (but not tetramers) and causes conformational changes in their core fold. Moreover, an allosteric mechanism facilitates exchange of H3-H4 between RbAp48 and ASF1. A complex network of factors with overlapping affinities represses splicing through intronic elements   pp36 - 45 Yang Wang, Xinshu Xiao, Jianming Zhang, Rajarshi Choudhury, Alex Robertson, Kai Li, Meng Ma, Christopher B Burge and Zefeng Wang doi:10.1038/nsmb.2459 A cell-based screen for intronic splicing silencers revealed ten sequence motifs that inhibited splicing in human cells and either enhanced or inhibited exon inclusion when inserted into exons. Identification of trans-acting splicing factors for each motif revealed a complex network, which suggests that cis elements function differently in distinct cellular contexts, depending on the regulatory factors present. Site-specific monoubiquitination activates Ras by impeding GTPase-activating protein function   pp46 - 52 Rachael Baker, Steven M Lewis, Atsuo T Sasaki, Emily M Wilkerson, Jason W Locasale, Lewis C Cantley, Brian Kuhlman, Henrik G Dohlman and Sharon L Campbell doi:10.1038/nsmb.2430 Post-translational modifications are one way in which GTPase functions can be regulated. Monoubiquitination of Lys147 of Ras has been shown to promote tumorigenesis. New data now indicate that this modification promotes Ras activation by impairing GTP hydrolysis catalyzed by GTPase-activating proteins. The structural basis of direct glucocorticoid-mediated transrepression   pp53 - 58 William H Hudson, Christine Youn and Eric A Ortlund doi:10.1038/nsmb.2456 Glucocorticoid receptor (GR) transactivates genes containing the response element GRE. GR can also mediate transrepression of genes by binding to the so-called negative GRE (nGRE). The interaction between GR and nGRE is now revealed by structural and functional approaches, showing that two GR monomers bind nGRE in a unique conformation and with strong negative cooperativity. Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy   pp59 - 66 Chinatsu Otomo, Zoltan Metlagel, Giichi Takaesu and Takanori Otomo doi:10.1038/nsmb.2431 The ATG12~ATG5 conjugate promotes the transfer of the ubiquitin-like protein LC3 to phosphatidylethanolamine (PE), a modification required for autophagosome formation. Structural and biochemical analyses reveal the determinants for ATG12~ATG5 binding to ATG16 and the E3 ligase ATG3, and indicate how the conjugate stimulates PE–LC3 formation. Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4    pp67 - 72 Xiaoai Zhang, Guangwen Lu, Jianxun Qi, Yan Li, Yan He, Xiang Xu, Jia Shi, Catherine W-H Zhang, Jinghua Yan and George F Gao doi:10.1038/nsmb.2432 Measles virus hemagglutinin (MVH) can bind to different cell surface receptors in the human host. CD46, the first identified MVH receptor, is used mainly by vaccine strains, whereas clinical strains can use SLAM on macrophages and dendritic cells and nectin-4 on epithelial cells. The crystal structure of MVH in complex with the outermost ectodomain of nectin-4 is now presented, revealing a potential target site for drug development. Eri1 degrades the stem-loop of oligouridylated histone mRNAs to induce replication-dependent decay   pp73 - 81 Kai P Hoefig, Nicola Rath, Gitta A Heinz, Christine Wolf, Jasmin Dameris, Aloys Schepers, Elisabeth Kremmer, K Mark Ansel and Vigo Heissmeyer doi:10.1038/nsmb.2450 The exoribonuclease Eri1 binds the stem-loop of histone mRNAs, but the functional significance of this interaction has been unclear. New studies now indicate that 3A oligouridylation of histone mRNAs enables the Lsm1–7 complex to bind the oligo(U) tail and to interact with Eri1, whose catalytic activity degrades the double-stranded stem-loop structure. The ATPase domain of ISWI is an autonomous nucleosome remodeling machine   pp82 - 89 Felix Mueller-Planitz, Henrike Klinker, Johanna Ludwigsen and Peter B Becker doi:10.1038/nsmb.2457 Previous work has implied that the ATPase domain of ISWI chromatin remodelers cooperates with a DNA-binding accessory domain to achieve remodeling. Quantitative biochemical analyses now reveal that the ATPase domain exists in two conformations and that DNA binding induces the catalytically active conformation. The ATPase domain has an intrinsic ability to bind and remodel nucleosomes, which suggests that it acts autonomously. See also: News and Views by Manning & Peterson HLA-DO acts as a substrate mimic to inhibit HLA-DM by a competitive mechanism   pp90 - 98 Abigail I Guce, Sarah E Mortimer, Taejin Yoon, Corrie A Painter, Wei Jiang, Elizabeth D Mellins and Lawrence J Stern doi:10.1038/nsmb.2460 HLA-DM interacts with MHCII and promotes peptide exchange. This activity of HLA-DM is regulated by HLA-DO. The crystal structure of the HLA-DO–HLA-DM complex along with mutagenesis and kinetic analyses reveal that HLA-DO adopts a classical MHCII structure and competitively inhibits HLA-DM's activity on MHCII. See also: News and Views by Denzin & Cresswell Architecture of the major component of the type III secretion system export apparatus   pp99 - 104 Patrizia Abrusci, Marta Vergara-Irigaray, Steven Johnson, Morgan D Beeby, David R Hendrixson, Pietro Roversi, Miriam E Friede, Janet E Deane, Grant J Jensen, Christoph M Tang and Susan M Lea doi:10.1038/nsmb.2452 The transmembrane export apparatus regulates protein secretion through bacterial type III secretion systems. New structural data indicate that MxiA, a major component of the apparatus, assembles in a nonameric ring. This and additional structural information provide a framework for understanding how protein secretion is controlled. Cryo-EM structure of the mature dengue virus at 3.5-Å resolution   pp105 - 110 Xiaokang Zhang, Peng Ge, Xuekui Yu, Jennifer M Brannan, Guoqiang Bi, Qinfen Zhang, Stan Schein and Z Hong Zhou doi:10.1038/nsmb.2463 Dengue virus has two membrane proteins, E and M, which undergo dramatic structural changes during the life cycle of the virus. The 3.5-Å cryo-EM structure of the mature prefusion Dengue virion reveals the detailed interactions between E and M, providing insight into how conformational changes are triggered. FMNL3 FH2–actin structure gives insight into formin-mediated actin nucleation and elongation   pp111 - 118 Morgan E Thompson, Ernest G Heimsath, Timothy J Gauvin, Henry N Higgs and F Jon Kull doi:10.1038/nsmb.2462 Formins regulate actin nucleation and filament elongation through their conserved FH2 domain. The formin FMNL3 induces assembly of filopodia, and now the crystal structure of its FH2 domain in complex with actin, together with functional analyses, provides insight into formin's activities. Analysis Top Multilayered chromatin analysis reveals E2f, Smad and Zfx as transcriptional regulators of histones   pp119 - 126 David Gokhman, Ilana Livyatan, Badi Sri Sailaja, Shai Melcer and Eran Meshorer doi:10.1038/nsmb.2448 A comprehensive metagenomic analysis of chromatin immunoprecipitation–sequencing and microarray analysis (ChIP-seq and ChIP-chip) data from mouse embryonic stem cells provides insight into how histone gene transcription is controlled. The work reveals a complex mode of regulation, with multiple factors acting to regulate transcription of core and linker histones. Resource Top Global analysis of yeast mRNPs   pp127 - 133 Sarah F Mitchell, Saumya Jain, Meipei She and Roy Parker doi:10.1038/nsmb.2468 mRNA-binding proteins have crucial regulatory functions in gene expression. A global analysis in budding yeast now uncovers 120 proteins that cross-link to mRNA, including 66 new mRNA-binding proteins. CLIP analyses of P-body components further identify sites of interaction on specific mRNAs, revealing principles by which these proteins assemble into P-body mRNPs. Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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