Nature Structural & Molecular Biology Contents: February 2013 Volume #20 pp 135 - 244

TABLE OF CONTENTS February 2013 Volume 20, Issue 2 Commentary News and Views Research Highlights Articles Analysis Corrigenda Errata Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Stem Cell Biology Special Issue and Web Focus The January special issue of Cell Research and the accompanying web focus on Stem Cell Biology delves into our current understanding and investigates recent advances in various aspects of stem cell biology, cell reprogramming, and their relevance to diseases. Access the Stem Cell Biology Special Issue today!   Commentary Top Coordinating the impact of structural genomics on the human α-helical transmembrane proteome   pp135 - 138 Ursula Pieper, Avner Schlessinger, Edda Kloppmann, Geoffrey A Chang, James J Chou, Mark E Dumont, Brian G Fox, Petra Fromme, Wayne A Hendrickson, Michael G Malkowski, Douglas C Rees, David L Stokes, Michael H B Stowell, Michael C Wiener, Burkhard Rost, Robert M Stroud, Raymond C Stevens and Andrej Sali doi:10.1038/nsmb.2508 Given the recent successes in determining membrane-protein structures, we explore the tractability of determining representatives for the entire human membrane proteome. This proteome contains 2,925 unique integral α-helical transmembrane-domain sequences that cluster into 1,201 families sharing more than 25% sequence identity. Structures of 100 optimally selected targets would increase the fraction of modelable human α-helical transmembrane domains from 26% to 58%, providing structure and function information not otherwise available. News and Views Top The COPII cage sharpens its image   pp139 - 140 Elizabeth A. Miller doi:10.1038/nsmb.2507 Self-assembly of the COPII coat proteins Sec13 and Sec31 creates a spherical cage that drives vesicle formation from the endoplasmic reticulum. A multipronged approach now provides a convincing pseudoatomic model of the assembled cage that sharpens our understanding of the architecture, contact sites and flexibility of this remarkable structure. See also: Article by Noble et al. Looking for a promoter in 3D   pp141 - 142 Vladimir Svetlov and Evgeny Nudler doi:10.1038/nsmb.2498 Direct time-resolved single-molecule observations of promoter search by Escherichia coli RNA polymerase indicate no evidence of facilitated diffusion, according to a new report. See also: Article by Wang et al. Research Highlights Splicing with super 8 | KRIT-ical interactions | Stressed ribosomes take the slow road Articles Interaction between FIP200 and ATG16L1 distinguishes ULK1 complex–dependent and –independent autophagy   pp144 - 149 Noor Gammoh, Oliver Florey, Michael Overholtzer and Xuejun Jiang doi:10.1038/nsmb.2475 A biochemical approach is used to understand how the ULK1 complex integrates signals from ATG proteins during autophagy. The interaction between ULK1-associated protein FIP200 and ATG16L1 of the ATG5 complex is revealed. This interaction is important for autophagy induced by amino acid starvation but not by glucose deprivation. HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation   pp150 - 158 Megan E Filbin, Breanna S Vollmar, Dan Shi, Tamir Gonen and Jeffrey S Kieft doi:10.1038/nsmb.2465 Studies of the hepatitis C virus internal ribosome entry site (IRES) mechanism have focused on how IRES assembles an 80S ribosome at the start codon. Structural and functional analyses demonstrate that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause conformational changes and that the mutated domain decreases IRES activity by inhibiting ribosome translocation and, thereby, translation elongation. Structural & Molecular Biology JOBS of the week PhD Position in Pollination Biology and Molecular Ecology Prof. Ian T. Baldwin, Department of Molecular Ecology, Max Plank Institute for Chemical Ecology Assistant Director of Genomic and Molecular Pathology Division The University of Chicago Postdoctoral Research Fellows in Molecular Crystal Simulations University of Southampton PhD positions in Molecular Life Sciences Max F. Perutz Laboratories (MFPL) Molecular Mechanisms of Autophagy: Postdoctoral Positions in Molecular Cell Biology Sabanci University 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 The voltage-dependent gate in MthK potassium channels is located at the selectivity filter   pp159 - 166 David J Posson, Jason G McCoy and Crina M Nimigean doi:10.1038/nsmb.2473 In order to locate the voltage-dependent gate in the MthK potassium channel, intracellular quaternary ammonium blockers are used for electrophysiology and crystallographic analyses. The data conclusively show that the inactivation gate is located at the selectivity filter and not at the cytoplasmic bundle crossing entrance. A pseudoatomic model of the COPII cage obtained from cryo-electron microscopy and mass spectrometry   pp167 - 173 Alex J Noble, Qian Zhang, Jason O'Donnell, Hanaa Hariri, Nilakshee Bhattacharya, Alan G Marshall and Scott M Stagg doi:10.1038/nsmb.2467 The COPII cage, formed by Sec13 and Sec31, organizes other proteins into a lattice on the endoplasmic-reticulum membrane and is involved in transporting cargo from the endoplasmic reticulum to the Golgi apparatus. A combination of cryo-EM and H/D-exchange MS analyses leads to a 12-Å-resolution model of the COPII cage, yielding insight into its architecture and assembly. See also: News and Views by Miller The promoter-search mechanism of Escherichia coli RNA polymerase is dominated by three-dimensional diffusion   pp174 - 181 Feng Wang, Sy Redding, Ilya J Finkelstein, Jason Gorman, David R Reichman and Eric C Greene doi:10.1038/nsmb.2472 The transcription machinery must locate specific promoter sequences among a vast excess of nonspecific DNA. Real-time single-molecule experiments with E. coli RNA polymerase, combined with theoretical calculations, suggest that facilitated diffusion does not contribute to promoter targeting at physiologically relevant protein concentrations but that instead the promoter search is dominated by three-dimensional diffusion. See also: News and Views by Svetlov & Nudler Nuclear receptor co-repressors are required for the histone-deacetylase activity of HDAC3 in vivo    pp182 - 187 Seo-Hee You, Hee-Woong Lim, Zheng Sun, Molly Broache, Kyoung-Jae Won and Mitchell A Lazar doi:10.1038/nsmb.2476 Histone deacetylase 3 (HDAC3) has low enzymatic activity in vitro unless associated with the nuclear receptor corepressors NCOR1 and SMRT through the deacetylase activation domain (DAD). Mice lacking functional DADs in both NCOR1 and SMRT are born and reach adulthood but lack HDAC3 activity, whereas mice lacking HDAC3 are embryonic lethal, which suggests an essential deacetylase-independent function of HDAC3. Dimer asymmetry defines a-catenin interactions   pp188 - 193 Erumbi S Rangarajan and Tina Izard doi:10.1038/nsmb.2479 The protein a-catenin has an essential role in stabilizing cell-cell junctions, and it is involved in multiple interactions with other cytoskeleton proteins. The crystal structure of nearly full-length human a-catenin now reveals a handshake-like dimer with the two monomers in distinct conformations. This dimer asymmetry is important for F-actin binding and for interactions with activated vinculin. Sequential primed kinases create a damage-responsive phosphodegron on Eco1    pp194 - 201 Nicholas A Lyons, Bryan R Fonslow, Jolene K Diedrich, John R Yates III and David O Morgan doi:10.1038/nsmb.2478 In budding yeast, EcoI acetylates cohesin to establish sister chromatid cohesion in S phase. EcoI is subsequently modified by the ubiquitin E3 ligase SCF-Cdc4 and rapidly degraded. New work shows how sequential phosphorylation by three independent kinases generates a binding site for SCF-Cdc4 to promote EcoI degradation, thereby coupling EcoI activity, and thus sister chromatid cohesion, to the cell cycle. Chromatin proteins captured by ChIP–mass spectrometry are linked to dosage compensation in Drosophila    pp202 - 209 Charlotte I Wang, Artyom A Alekseyenko, Gary LeRoy, Andrew EH Elia, Andrey A Gorchakov, Laura-Mae P Britton, Stephen J Elledge, Peter V Kharchenko, Benjamin A Garcia and Mitzi I Kuroda doi:10.1038/nsmb.2477 The MSL complex acts on chromatin to and is required for X-chromosome dosage compensation. Chromatin-interacting protein MS (ChIP-MS) is now used to identify proteins and histone modifications interacting with the MSL complex, leading to the identification of CG4747. Functional analysis indicates that this protein is involved in targeting MSL to H3K36me3-containing chromatin. Conformational heterogeneity of the aspartate transporter GltPh    pp210 - 214 Inga Hänelt, Dorith Wunnicke, Enrica Bordignon, Heinz-Jürgen Steinhoff and Dirk Jan Slotboom doi:10.1038/nsmb.2471 GltPh is a homotrimeric Na+-coupled aspartate transporter that belongs to the glutamate transporter family. The conformational changes that occur during GltPh transport are now directly observed using EPR spectroscopy, revealing that the transporting domains sample multiple states, regardless of the presence of substrate or ions. Conformational ensemble of the sodium-coupled aspartate transporter   pp215 - 221 Elka R Georgieva, Peter P Borbat, Christopher Ginter, Jack H Freed and Olga Boudker doi:10.1038/nsmb.2494 The sodium and aspartate symporter GltPh mediates transport by alternating between outward-facing and inward-facing states. These conformational changes are now probed using double electron-electron resonance (DEER) spectroscopy. The data show that GltPh samples both states with similar probabilities, and that each protomer in the GltPh homotrimer behaves independently of the others. Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains   pp222 - 229 Swetansu K Hota, Saurabh K Bhardwaj, Sebastian Deindl, Yuan-chi Lin, Xiaowei Zhuang and Blaine Bartholomew doi:10.1038/nsmb.2486 The ISWI chromatin remodelers interact with extranucleosomal DNA to mediate nucleosome positioning. A new study now shows that the conserved SLIDE domain in the Isw2 subunit, which binds linker DNA, facilitates unidirectional linker DNA movement into nucleosomes. These findings suggest that the SLIDE domain functions in conjunction with the ATPase domain to mobilize nucleosomes. Complexes of HIV-1 RT, NNRTI and RNA/DNA hybrid reveal a structure compatible with RNA degradation   pp230 - 236 Mikalai Lapkouski, Lan Tian, Jennifer T Miller, Stuart F J Le Grice and Wei Yang doi:10.1038/nsmb.2485 Crystal structures of HIV-1 reverse transcriptase (RT) bound to an RNA/DNA hybrid (without any cross-linking) and in the presence of non-nucleotide RT inhibitors (NNRTIs) nevirapine and efavirenz are now reported. The structures show the RNA/DNA hybrid in a previously unseen conformation with ready access to the RNase-H active site of RT. Analysis Top Evolutionary conservation of codon optimality reveals hidden signatures of cotranslational folding   pp237 - 243 Sebastian Pechmann and Judith Frydman doi:10.1038/nsmb.2466 Rare or nonoptimal codons that cause ribosomes to pause have been suggested to be important determinants of cotranslational folding. A revised translational efficiency scale, which considers tRNA abundance as well as codon usage and codon-tRNA interaction, now suggests a correlation between optimal or nonoptimal codon usage and secondary structure of the nascent polypeptide. Corrigenda Top The resistance of DMC1 D-loops to dissociation may account for the DMC1 requirement in meiosis   p244 Dmitry V Bugreev, Roberto J Pezza, Olga M Mazina, Oleg N Voloshin, R Daniel Camerini-Otero and Alexander V Mazin doi:10.1038/nsmb0213-244a H3K36me3 key to Polycomb-mediated gene silencing in lineage specification   p244 Jumana AlHaj Abed and Richard S. Jones doi:10.1038/nsmb0213-244b A transcription factor-based mechanism for mouse heterochromatin formation   p244 Aydan Bulut-Karslioglu, Valentina Perrera, Manuela Scaranaro, Inti Alberto de la Rosa-Velazquez, Suzanne van de Nobelen, Nicholas Shukeir, Johannes Popow, Borbala Gerle, Susanne Opravil, Michaela Pagani, Simone Meidhof, Thomas Brabletz, Thomas Manke, Monika Lachner and Thomas Jenuwein doi:10.1038/nsmb0213-244c Errata Top Tudor domain ERI-5 tethers an RNA-dependent RNA polymerase to DCR-1 to potentiate endo-RNAi   p244 Caroline Thivierge, Neetha Makil, Mathieu Flamand, Jessica J Vasale, Craig C Mello, James Wohlschlegel, Darryl Conte Jr and Thomas F Duchaine doi:10.1038/nsmb0213-244d The spindle-assembly checkpoint and the beauty of self-destruction   p244 Andrea Musacchio and Andrea Ciliberto doi:10.1038/nsmb0213-244e Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1α   p244 Nausica Arnoult, Amandine Van Beneden and Anabelle Decottignies doi:10.1038/nsmb0213-244f 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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