Nature Structural & Molecular Biology Contents: June 2013 Volume #20 pp 645- 768

TABLE OF CONTENTS June 2013 Volume 20, Issue 6 News and Views Research Highlights Perspective Articles Brief Communications Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Combining open-access publishing with a powerful networking platform. The Frontiers publication process and Research Networking Platform allow you to build your own scientific profiles while following the work of colleagues, mentors and your science heroes. Connect with your community today   News and Views Top Toggling in the spliceosome   pp645 - 647 John Abelson doi:10.1038/nsmb.2603 Two structural variants of the RNaseH-like domain of the highly conserved spliceosomal protein Prp8 are correlated with Prp8 mutants that stabilize either the first- or second-step active sites of the spliceosome. See also: Article by Schellenberg et al. Solo or doppio: how many CENP-As make a centromeric nucleosome?   pp648 - 650 Elaine M Dunleavy, Weiguo Zhang and Gary H Karpen doi:10.1038/nsmb.2602 Whether centromere-specific CENP-A-containing nucleosomes comprise one molecule each of CENP-A and histones H4, H2A and H2B (forming a tetramer or hemisome) or two molecules of all four histones (forming an octamer) has been controversial. Three new studies now address this controversy using complementary in vitro and in vivo approaches. See also: Article by Hasson et al. | Brief Communication by Miell et al. Making sense of nonsense   pp651 - 653 Matthias W Hentze and Elisa Izaurralde doi:10.1038/nsmb.2601 Eukaryotic mRNAs containing nonsense codons are degraded by nonsense-mediated mRNA decay (NMD). In humans, NMD was proposed to act exclusively on newly synthesized mRNA during a 'pioneer round' of translation, when mRNA is associated with the nuclear cap-binding complex (CBC). Two reports now challenge this view, revealing that NMD is independent of whether CBC or the cytoplasmic cap-binding protein (eIF4E) promotes translation and can occur later in an mRNA's life. See also: Article by Durand & Lykke-Andersen | Article by Rufener & Mühlemann This is about the in and the out   pp654 - 655 Peter J F Henderson and Stephen A Baldwin doi:10.1038/nsmb.2604 At last, structures have been solved for different conformational states, facing in and facing out, for the same transporter protein of the major facilitator superfamily. The structural basis of alternating substrate access for binding and translocation can now be properly visualized. See also: Brief Communication by Quistgaard et al. Structural & Molecular Biology JOBS of the week POSTDOC in Cardiopulmonary Molecular Biology Hannover Medical School, Germany Full Professorship (W2) for Molecular Mircrobiology Johann Wolfgang Goethe University Frankfurt Postdoctoral Position in Molecular Neuroscience The University of Iowa Post doctoral fellow- Molecular evolution of membrane bound proteins Uppsala University, Department of Neuroscience Post Doctoral Fellow Aaron Diamond AIDS Research Center 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 Research Highlights Top Getting your vitamins—out | mTOR: restricted access Perspective Top Scratching the (lateral) surface of chromatin regulation by histone modifications   pp657 - 661 Philipp Tropberger and Robert Schneider doi:10.1038/nsmb.2581 Whereas post-translational modifications (PTMs) in histone tails are well characterized, functional and mechanistic insights into PTMs in the globular nucleosome core have been lacking. This Perspective covers recent advances in the understanding of lateral-surface PTMs and their effects on nucleosome and chromatin dynamics. Articles Top Substrate-specific structural rearrangements of human Dicer    pp662 - 670 David W Taylor, Enbo Ma, Hideki Shigematsu, Michael A Cianfrocco, Cameron L Noland, Kuniaki Nagayama, Eva Nogales, Jennifer A Doudna and Hong-Wei Wang doi:10.1038/nsmb.2564 Human Dicer can process long double-stranded RNA and hairpin precursor RNA to yield short interfering RNAs or microRNAs, respectively. EM and single-particle analyses of Dicer–substrate complexes now provide insight into the structural basis of Dicer's substrate preference, implicating RNA structure and cofactors in determining substrate recognition and processing efficiency by Dicer. Telomere position effect regulates DUX4 in human facioscapulohumeral muscular dystrophy   pp671 - 678 Guido Stadler, Fedik Rahimov, Oliver D King, Jennifer C J Chen, Jerome D Robin, Kathryn R Wagner, Jerry W Shay, Charles P Emerson Jr and Woodring E Wright doi:10.1038/nsmb.2571 The telomere position effect (TPE) can change gene expression at intermediate telomere lengths in cultured human cells, but it has not been previously implicated in disease pathogenesis. A gene implicated in facioscapulohumeral muscular dystrophy (FSHD) pathogenesis, and located adjacent to a chromosome end, is now shown to be upregulated in muscle cells with short telomeres, which suggests that TPE contributes to the late-onset phenotype of FSHD. Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment   pp679 - 686 Alf Honigmann, Geert van den Bogaart, Emilio Iraheta, H Jelger Risselada, Dragomir Milovanovic, Veronika Mueller, Stefan Müllar, Ulf Diederichsen, Dirk Fasshauer, Helmut Grubmüller, Stefan W Hell, Christian Eggeling, Karin Kühnel and Reinhard Jahn doi:10.1038/nsmb.2570 Interactions between synaptotagmin-1 and the SNARE syntaxin-1 are known to mediate synaptic-vesicle exocytosis. Fusion experiments with artificial lipid membranes combined with the crystal structure of synaptotagmin's C2B domain bound to phosphoserine indicate that PIP2 clusters, organized by syntaxin, act as molecular beacons for vesicle docking and direct Ca2+-dependent membrane fusion. The octamer is the major form of CENP-A nucleosomes at human centromeres   pp687 - 695 Dan Hasson, Tanya Panchenko, Kevan J Salimian, Mishah U Salman, Nikolina Sekulic, Alicia Alonso, Peter E Warburton and Ben E Black doi:10.1038/nsmb.2562 Centromere protein A (CENP-A) is a histone H3 variant that specifies centromere location, but the histone composition and stoichiometry of CENP-A nucleosomes have been controversial. ChIP-seq and biochemical analyses of in vitro–reconstituted CENP-A nucleosomes now demonstrate that the predominant form at functional centromeres is an octamer with loose DNA ends. See also: News and Views by Dunleavy et al. Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming   pp696 - 701 Elena Maspero, Eleonora Valentini, Sara Mari, Valentina Cecatiello, Paolo Soffientini, Sebastiano Pasqualato and Simona Polo doi:10.1038/nsmb.2566 HECT E3 ligases directly catalyze ubiquitin transfer to their substrates. The crystal structure of ubiquitin-loaded Nedd4 HECT domain in complex with ubiquitin is now presented, revealing insights into the mechanisms for catalytic priming and sequential addition and suggesting the basis for Lys63 specificity. Nonsense-mediated mRNA decay occurs during eIF4F-dependent translation in human cells   pp702 - 709 Sébastien Durand and Jens Lykke-Andersen doi:10.1038/nsmb.2575 It has been suggested that nonsense-mediated mRNA decay (NMD) is restricted to a pioneer round of translation initiated on mRNAs associated with the cap-binding complex (CBC), whereas the exchange of the CBC for the eIF4F translation initiation complex renders mRNAs immune to NMD. However, multiple lines of evidence now suggest that eIF4F-associated mRNAs are not immune to NMD. See also: News and Views by Hentze & Izaurralde eIF4E-bound mRNPs are substrates for nonsense-mediated mRNA decay in mammalian cells   pp710 - 717 Simone C Rufener and Oliver Mühlemann doi:10.1038/nsmb.2576 It has been suggested that nonsense-mediated mRNA decay (NMD) is restricted to cap-binding complex (CBC)-bound mRNAs during the pioneer round of translation in mammalian cells. However, analysis of the decay kinetics of mRNAs bound to either CBC or the eukaryotic initiation factor 4E in human cells shows that both substrate types are equally susceptible to NMD. See also: News and Views by Hentze & Izaurralde Coordinated conformational and compositional dynamics drive ribosome translocation   pp718 - 727 Jin Chen, Alexey Petrov, Albert Tsai, Seán E O'Leary and Joseph D Puglisi doi:10.1038/nsmb.2567 During translation, elongation factor G (EF-G) and transfer RNAs alternately bind the ribosome to direct protein synthesis. Using single-molecule fluorescence with zero-mode waveguide, EF-G–GTP is shown to continuously sample both rotational states of the ribosome, binding with higher affinity to the rotated state to stimulate translocation and return to the nonrotated state. A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation   pp728 - 734 Matthew J Schellenberg, Tao Wu, Dustin B Ritchie, Sebastian Fica, Jonathan P Staley, Karim A Atta, Paul LaPointe and Andrew M MacMillan doi:10.1038/nsmb.2556 The core of the spliceosome contains PRP8, a highly conserved protein that contacts each of the active site components and is implicated in both steps of pre-mRNA splicing. New work shows that structural rearrangement of the PRP8 RNase H domain between the first and second steps forms a Mg2+-binding site that is required for the second splicing reaction, revealing the molecular basis of the two-state model of splicing catalysis. See also: News and Views by Abelson Structural basis for the recruitment of the human CCR4–NOT deadenylase complex by tristetraprolin    pp735 - 739 Marc R Fabian, Filipp Frank, Christopher Rouya, Nadeem Siddiqui, Wi S Lai, Alexey Karetnikov, Perry J Blackshear, Bhushan Nagar and Nahum Sonenberg doi:10.1038/nsmb.2572 Tristetraprolin (TTP) post-transcriptionally represses gene expression by interacting with AU-rich elements in 3A untranslated regions of target mRNAs and mediates deadenylation and decay by recruiting the CCR4–NOT deadenylase complex through the CNOT1 subunit. Structural and mutational studies now show how the TTP-CNOT1 interaction brings about TTP-mediated deadenylation of target mRNAs. Studies of IscR reveal a unique mechanism for metal-dependent regulation of DNA binding specificity   pp740 - 747 Senapathy Rajagopalan, Sarah J Teter, Petrus H Zwart, Richard G Brennan, Kevin J Phillips and Patricia J Kiley doi:10.1038/nsmb.2568 The bacterial metalloregulator IscR possesses the unusual ability to direct differential gene expression via specific recognition of two distinct operator motifs in an Fe-S–dependent manner. New work shows that Fe-S binding displaces a residue required for sequence discrimination at the DNA binding interface, revealing a conditional, ligand-mediated mechanism regulating sequence-specific recognition. Preferential D-loop extension by a translesion DNA polymerase underlies error-prone recombination   pp748 - 755 Richard T Pomerantz, Isabel Kurth, Myron F Goodman and Mike E O'Donnell doi:10.1038/nsmb.2573 Genetic evidence has implicated the SOS-induced translesion DNA polymerase DinB (Pol IV) in error-prone recombination. Now biochemical analyses show that Pol IV outcompetes high-fidelity polymerases during the extension of D-loop recombination intermediates under SOS response conditions, providing new insight into the mechanism of stress-induced mutations in Escherichia coli. The microtubule-associated tau protein has intrinsic acetyltransferase activity   pp756 - 762 Todd J Cohen, Dave Friedmann, Andrew W Hwang, Ronen Marmorstein and Virginia M Y Lee doi:10.1038/nsmb.2555 Tau is a microbutule-associated protein that can form pathological aggregates in neurodegenerative conditions such as Alzheimer's disease. Tau can undergo acetylation at lysine residues within its microtubule-binding repeats, a modification that impairs tau function and promotes its aggregation. Now tau is identified as an acetyltransferase able to modify itself. Brief Communications Top CENP-A confers a reduction in height on octameric nucleosomes   pp763 - 765 Matthew D D Miell, Colin J Fuller, Annika Guse, Helena M Barysz, Andrew Downes, Tom Owen-Hughes, Juri Rappsilber, Aaron F Straight and Robin C Allshire doi:10.1038/nsmb.2574 Centromere protein A (CENP-A) is a histone H3 variant that specifies centromere location. Their reduced height relative to canonical H3 nucleosomes suggested that CENP-A nucleosomes might be tetrameric, but new biophysical measurements of reconstituted nucleosomes show that CENP-A confers a reduction in height on octameric CENP-A nucleosomes. See also: News and Views by Dunleavy et al. Structural basis for substrate transport in the GLUT-homology family of monosaccharide transporters   pp766 - 768 Esben M Quistgaard, Christian Löw, Per Moberg, Lionel Trésaugues and Pär Nordlund doi:10.1038/nsmb.2569 The bacterial transporter XylE is a member of the major facilitator family (MFS). The structure of XylE in its partially occluded outward-facing state was recently solved. Now the same transporter is captured in different conformational states, inward open and partially occluded inward open, thus providing insights into the transport cycle of MFS transporters. See also: News and Views by Henderson & Baldwin Top Advertisement Choose Scientific Reports for fast, efficient, open access publishing 93% of authors said they are likely or very likely to recommend Scientific Reports to their colleagues* 92% of authors would publish in Scientific Reports again* SUBMIT your paper today! *Nature Publishing Group author survey, data correct as of April 2013   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. 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