Nature Structural & Molecular Biology Contents: August 2013 Volume #20 pp 915-1017

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TABLE OF CONTENTS August 2013 Volume 20, Issue 8 News and Views Research Highlights Articles Brief Communication Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Reprint Collection MicroRNAs from bench to clinic This Nature Reprint Collection presents some of the recent advances in moving microRNAs from basic research into the clinic both as diagnostic biomarkers and therapeutic targets.  Click here to access the Collection for free!   Produced with support from:     News and Views Top Voltage-coupled conformational dynamics of mitochondrial protein-import channel   pp915 - 917 Martin van der Laan, Sandra G Schrempp and Nikolaus Pfanner doi:10.1038/nsmb.2643 Mitochondria contain multisubunit translocases to import preproteins from the cytosol. The presequence translocase of the inner membrane operates in a voltage-gated manner, but how a preprotein-conducting channel responds to the membrane potential was unknown. A new study identifies a voltage-coupled conformational change in a transmembrane segment of the Tim23 import channel, representing a major step toward understanding the molecular basis of a voltage-gated protein translocase. See also: Article by Malhotra et al. Conformational dynamics of STIM1 activation   pp918 - 919 Stefan Feske and Murali Prakriya doi:10.1038/nsmb.2647 The binding of stromal interaction molecule 1 (STIM1) to ORAI calcium channels is critical for store-operated calcium entry (SOCE), a calcium influx pathway conserved among nearly all vertebrate cells. Although many major steps of this pathway are well understood, crucial details regarding the mechanism of STIM1 activation remain unclear. A study in this issue provides important new insights into the conformational changes that occur during STIM1 activation. See also: Article by Zhou et al. A molecular motor finds its track   pp920 - 921 Jared C Cochran and F Jon Kull doi:10.1038/nsmb.2644 The detailed mechanism by which the molecular motors kinesin and myosin travel along their respective protein tracks as they generate force during motile processes is still poorly understood. In a recent breakthrough, a crystal structure of kinesin in complex with tubulin illuminates the atomic-level details of a motor-track interaction, answering many questions yet leaving a number of mysteries unresolved. See also: Article by Gigant et al. Structural & Molecular Biology JOBS of the week POSTDOC in Cardiopulmonary Molecular Biology Hannover Medical School (MHH) Postdoctoral Position in Molecular Biology and Drug Discovery Moffitt Cancer Center & Research Institute Postdoctoral Research Associate Pool University of Oregon, Institute of Ecology and Evolution Senior Research Technologist St. Jude Children's Research Hospital Postdoctoral fellow University of California, Riverside More Science jobs from Research Highlights Top NPCs, super-resolved | A funnel-like viroporin | DNA pol in action Articles Top Polyadenylation site–induced decay of upstream transcripts enforces promoter directionality   pp923 - 928 Evgenia Ntini, Aino I Järvelin, Jette Bornholdt, Yun Chen, Mette Boyd et al. doi:10.1038/nsmb.2640 Most mammalian promoters are inherently bidirectional, but transcription only elongates productively in one direction. Data presented in this paper demonstrate that at least part of the answer lies in the asymmetric distribution of polyadenylation-site sequences around human gene promoters causing termination of upstream antisense transcription. Structure and function of Hip, an attenuator of the Hsp70 chaperone cycle   pp929 - 935 Zhuo Li, F Ulrich Hartl and Andreas Bracher doi:10.1038/nsmb.2608 The protein Hip interacts with chaperone Hsp70 and slows ADP dissociation from Hsp70, thus resulting in a delay in substrate release. Now crystal structures of Hip domains alone or in complex with Hsp70 nucleotide-binding domain, along with biochemical analyses, explain how Hip performs its activities. Translation-dependent displacement of UPF1 from coding sequences causes its enrichment in 3′ UTRs   pp936 - 943 David Zünd, Andreas R Gruber, Mihaela Zavolan and Oliver Mühlemann doi:10.1038/nsmb.2635 The RNA helicase UPF1 has been implicated in various functions including nonsense-mediated decay (NMD). Transcriptome-wide analysis of UPF1-binding sites in translationally active versus inhibited cells provides evidence for translation-independent UPF1-RNA interactions and also suggests that UPF1 bound to coding sequence may be displaced by translating ribosomes and that NMD substrate selection may occur after UPF1-RNA interaction. Cryo-EM structure of a helicase loading intermediate containing ORC–Cdc6–Cdt1–MCM2-7 bound to DNA   pp944 - 951 Jingchuan Sun, Cecile Evrin, Stefan A Samel, Alejandra Fernández-Cid, Alberto Riera et al. doi:10.1038/nsmb.2629 Eukaryotic DNA replication begins with recruitment of the ring helicase MCM2-7 by the origin recognition complex (ORC) in a reaction facilitated by initiation factors Cdc6 and Cdt1. A new cryo-EM structure of a helicase loading intermediate, the ORC–Cdc6–Cdt1–MCM2-7 complex, unexpectedly reveals both MCM2-7 and ORC hexamers encircling the DNA, and shows the arrangement of all 14 subunits within the helicase-loader complex. Single-molecule reconstitution of mRNA transport by a class V myosin   pp952 - 957 Thomas E Sladewski, Carol S Bookwalter, Myoung-Soon Hong and Kathleen M Trybus doi:10.1038/nsmb.2614 How a class V myosin transports mRNA is not well understood. Single-molecule reconstitution of messenger ribonucleoprotein complexes from purified proteins and a localizing mRNA in budding yeast demonstrates that the mRNA is instrumental in ensuring a stable, processive transport complex, whereas the number of localizing elements ('zip codes') influences run length and frequency. Structurally encoded intraclass differences in EphA clusters drive distinct cell responses   pp958 - 964 Elena Seiradake, Andreas Schaupp, Daniel del Toro Ruiz, Rainer Kaufmann, Nikolaos Mitakidis et al. doi:10.1038/nsmb.2617 Given the high degree of similarity between Eph receptors, it has remained unclear how the same ligand can produce different signaling outcomes. The crystal structures of apo and ligand-bound EphA4, combined with cellular assays with chimeric ectodomains, now indicate that the specificity of signaling outcome is largely dictated by clustering properties structurally encoded within the ectodomain. Structural changes in the mitochondrial Tim23 channel are coupled to the proton-motive force   pp965 - 972 Ketan Malhotra, Murugappan Sathappa, Judith S Landin, Arthur E Johnson and Nathan N Alder doi:10.1038/nsmb.2613 The mitochondrial inner membrane generates a proton-motive force (PMF) that drives cellular processes. Using a high-resolution fluorescence mapping approach combined with kinetic analyses, changes in the PMF are now shown to drive marked structural changes in the Tim23 channel of the TIM23 protein-translocation complex that are important for channel gating. See also: News and Views by van der Laan et al. Initial activation of STIM1, the regulator of store-operated calcium entry   pp973 - 981 Yubin Zhou, Prasanna Srinivasan, Shiva Razavi, Sam Seymour, Paul Meraner et al. doi:10.1038/nsmb.2625 In immune cells, CRAC channels in the plasma membrane regulate store-operated Ca2+ entry in response to STIM1, a sensor protein located in the endoplasmic reticulum (ER) membrane. New biophysical assays show how dimerization of STIM1's ER-luminal domains causes extension of its cytoplasmic domains toward the plasma membrane to contact the ORAI pore and activate the channel, revealing the structural dynamics of this Ca2+-signaling mechanism. See also: News and Views by Feske & Prakriya Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3   pp982 - 986 Hao Dou, Lori Buetow, Gary J Sibbet, Kenneth Cameron and Danny T Huang doi:10.1038/nsmb.2621 In dimeric RING E3 ligases, the tail domain of the second subunit primes the transfer reaction. The crystal structure of human Tyr363-phosphorylated CBL-B in complex with ubiquitin-linked E2 UbcH5Band a peptide substrate now shows that a phosphorylated residue can act as the priming element in monomeric RING E3s. Crystal structure of peroxisomal targeting signal-2 bound to its receptor complex Pex7p–Pex21p   pp987 - 993 Dongqing Pan, Toru Nakatsu and Hiroaki Kato doi:10.1038/nsmb.2618 Localization of protein to the peroxisome occurs through the recognition of specific targeting sequences (PTS1 or PTS2). The crystal structure of a yeast Pex7–Pex21 recognition complex bound to PTS2 reveals that the receptor complex forms a cavity with surfaces properties that complement the charge distribution on PTS2 and explain the conserved features of the peroxisomal targeting system. Noncoding RNAs prevent spreading of a repressive histone mark   pp994 - 1000 Claudia Keller, Raghavendran Kulasegaran-Shylini, Yukiko Shimada, Hans-Rudolf Hotz and Marc Bühler doi:10.1038/nsmb.2619 HP1 proteins bind methylated histone H3 Lys9, a hallmark of heterochromatin, and mediate heterochromatin spreading by recruiting histone methyltransferase activities. New studies have now identified a long noncoding RNA called BORDERLINE that prevents spreading of the HP1 protein Swi6 and histone H3 Lys9 methylation beyond the pericentromeric repeat region of fission yeast chromosome 1. Structure of a kinesin–tubulin complex and implications for kinesin motility   pp1001 - 1007 Benoît Gigant, Weiyi Wang, Birgit Dreier, Qiyang Jiang, Ludovic Pecqueur et al. doi:10.1038/nsmb.2624 Combined with kinetic analyses, the high resolution structure of kinesin-1 bound to a tubulin dimer offers a much-anticipated view of the motor-microtubule interface that illuminates the key step of neck-linker docking and of the structural basis for microtubule-accelerated ATP hydrolysis and motility. See also: News and Views by Cochran & Kull High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation   pp1008 - 1014 Madhanagopal Anandapadamanaban, Cecilia Andresen, Sara Helander, Yoshifumi Ohyama, Marina I Siponen et al. doi:10.1038/nsmb.2611 The general transcription factor TFIID comprises TATA-binding protein (TBP) and TBP-associated factors (TAFs). The high-resolution structure of yeast TBP in complex with yeast TAF1 containing both transcriptionally activating and repressing regions reveals detailed and specific molecular patterns of interactions with TBP and their significance for transcriptional regulation. Brief Communication Top The crystal structure of the eukaryotic 40S ribosomal subunit in complex with eIF1 and eIF1A   pp1015 - 1017 Melanie Weisser, Felix Voigts-Hoffmann, Julius Rabl, Marc Leibundgut and Nenad Ban doi:10.1038/nsmb.2622 Initiation factors eIF1 and eIF1A are key determinants of ribosomal scanning and initiation-codon selection during translation initiation. The structure of Tetrahymena thermophila 40S ribosome in complex with eIF1 and eIF1A reveals the conformational changes that accompany initiation-factor binding and provides new insights into the mechanism of start-codon recognition. Top Advertisement Still No. 1 in the field Molecular Psychiatry is proud to announce its new Impact Factor of 14.897. 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