Nature Structural & Molecular Biology Contents: July 2012 Volume #19 pp 657 - 736

Advertisement EXPERIENCE SUPERIOR X-RAY DATA QUALITY You can try out Agilent’s SuperNova and PX Scanner single-crystal X-ray crystallography systems, both equipped with our brightest ever 2nd generation Nova Cu source, at one of our state-of-the-art X-ray Centers of Excellence. Take a virtual tour of our Center of Excellence in California and register your interest in collecting data on your own samples. TABLE OF CONTENTS July 2012 Volume 19, Issue 7 News and Views Research Highlights Articles Brief Communications Technical Report Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement   News and Views Top The true core of RNA silencing revealed   pp657 - 660 Hiroshi M Sasaki and Yukihide Tomari doi:10.1038/nsmb.2302 RNA silencing is a sequence-specific gene regulation system conserved in eukaryotes, at the core of which lies the Argonaute protein family. Crystallographic studies of eukaryotic Argonaute proteins now reveal remarkably similar overall structures to their prokaryotic homologs while shedding new light on the fundamental relationship between their conformational dynamics and sophisticated strategies to silence specific targets. PARP pairs up to PARsylate   pp660 - 661 Nicolas Coquelle and J N Mark Glover doi:10.1038/nsmb.2306 New structural analyses suggest two different models for poly(ADP-ribose) polymerase 1 (PARP1) activation by single- and double-strand DNA breaks, providing evidence for PARP1 activation in cis and in trans. See also: Article by Ali et al. Nef-arious goings-on at the Golgi   pp661 - 662 James H Hurley and Juan S Bonifacino doi:10.1038/nsmb.2304 HIV-1 avoids the immune detection of infected cells by preventing class I molecules of the major histocompatibility complex (MHC-I) bound to viral peptides from reaching the cell surface. A new structure shows how Nef turns MHC-I from a noncargo into a cargo for the clathrin adaptor AP-1, thus directing MHC-I to the lysosome instead of the plasma membrane. See also: Article by Jia et al. Research Highlights The silence of the plants | Telomere overhang processing | Smaller and brighter Structural & Molecular Biology JOBS of the week Experimental test and analytical models for confinement of structural elements by innovative techniques Università degli Studi di Messina Postdoc - Structural Biology Duke University Postdoctoral Position in Structural Bioinformatics National Institute of Allergy and Infectious Diseases (NIAID) Processing of functional and structural RM data in extrapiramidal desorders Università di Pisa Post-doctoral Training Fellow - Divisions of Structural and Cancer Biology The Institute of Cancer Research More Science jobs from Structural & Molecular Biology EVENT X-Ray Methods in Structural Biology 15th - 30th Oct 2012 US More science events from Articles Top Intronic RNAs mediate EZH2 regulation of epigenetic targets   pp664 - 670 Sònia Guil, Marta Soler, Anna Portela, Jordi Carrère, Elena Fonalleras, Antonio Gómez, Alberto Villanueva and Manel Esteller doi:10.1038/nsmb.2315 Noncoding RNAs have been implicated in targeting the repressive polycomb complex PRC2 to specific genomic sites. In vivo cross-linking studies now reveal a number of intronic RNA sequences capable of binding the EZH2 subunit of PRC2 in human cancer cells and downregulating transcription of the SMYD3 histone methyltransferase gene, among others. Overexpression of an EZH2-interacting RNA was found to counteract tumorigenicity. Duplex interrogation by a direct DNA repair protein in search of base damage   pp671 - 676 Chengqi Yi, Baoen Chen, Bo Qi, Wen Zhang, Guifang Jia, Liang Zhang, Charles J Li, Aaron R Dinner, Cai-Guang Yang and Chuan He doi:10.1038/nsmb.2320 Mammalian dioxygenase ALKBH2 mediates direct oxidative repair of alkylation DNA lesions. Structural, biochemical and computational approaches are now used to reveal that ALKBH2 probes base pair stability by inserting a hydrophobic hairpin motif into the DNA duplex and does not need a damage-checking site, in contrast to DNA glycosylases. Structural dynamics of the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase    pp677 - 684 Andrés Palencia, Thibaut Crépin, Michael T Vu, Tommie L Lincecum Jr, Susan A Martinis and Stephen Cusack doi:10.1038/nsmb.2317 Leucyl-tRNA synthetase (LeuRS) synthesizes and then proofreads leucyl-tRNALeu for accurate protein synthesis. Structural analysis of Escherichia coli LeuRS reveals that the editing domain unexpectedly stabilizes the tRNA during aminoacylation and that translocation of the leucyl-tRNALeu from the aminoacylation site to the editing site requires correlated movements of several LeuRS domains. The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks   pp685 - 692 Ammar A E Ali, Gyula Timinszky, Raquel Arribas-Bosacoma, Marek Kozlowski, Paul O Hassa, Markus Hassler, Andreas G Ladurner, Laurence H Pearl and Antony W Oliver doi:10.1038/nsmb.2335 PARP1 is activated by sensing DNA damage, forming ADP-ribose chains that recruit DNA repair and chromatin remodeling factors. PARP1 recognizes DNA damage through its DNA-binding domain, which contains two zinc-finger regions (ZnF1 and ZnF2). The crystal structure of human PARP1-DBD bound to a DNA break reveals a dimeric arrangement, in which ZnF1 from one monomer interacts with ZnF2 from the other monomer, to recognize the DNA strand break. See also: News and Views by Coquelle & Glover Structure of Mre11–Nbs1 complex yields insights into ataxia-telangiectasia–like disease mutations and DNA damage signaling   pp693 - 700 Christian B Schiller, Katja Lammens, Ilaria Guerini, Britta Coordes, Heidi Feldmann, Florian Schlauderer, Carolin Möckel, Alexandra Schele, Katja Strässer, Stephen P Jackson and Karl-Peter Hopfner doi:10.1038/nsmb.2323 The Mre11–Rad50–Nbs1 (MRN) complex plays a central role in DNA damage signaling. The crystal structures of the Schizosaccharomyces pombe Mre11 catalytic domain in its apo form and in complex with a fragment of Nbs1 are now reported. Along with functional analyses, the work provides insight into checkpoint signaling and ATM activation as well as a framework to understand disease-related mutations. Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef pp701 - 706 Xiaofei Jia, Rajendra Singh, Stefanie Homann, Haitao Yang, John Guatelli and Yong Xiong doi:10.1038/nsmb.2328 The HIV-1 Nef protein associates with the cytoplasmic domain of class I MHC and with the µ1 subunit of clathin adaptor protein complex I, rerouting MHC I to the endolysosomal degradation pathway. The molecular mechanism for this effect is now revealed by the crystal structure of Nef together with MHC I and a domain from µ1. See also: News and Views by Hurley & Bonifacino Structural basis for heteromeric assembly and perinuclear organization of keratin filaments   pp707 - 715 Chang-Hun Lee, Min-Sung Kim, Byung Min Chung, Daniel J Leahy and Pierre A Coulombe doi:10.1038/nsmb.2330 Keratins form heterodimers that assemble into intermediate filaments. The structure of a central coiled-coil region formed between keratins 5 and 14 provides a new understanding of intermediate-filament architecture and assembly. Cellular data suggest a role for disulfide bridges in filament organization. Brief Communications Top AMP-activated protein kinase undergoes nucleotide-dependent conformational changes   pp716 - 718 Lei Chen, Jue Wang, Yuan-Yuan Zhang, S Frank Yan, Dietbert Neumann, Uwe Schlattner, Zhi-Xin Wang and Jia-Wei Wu doi:10.1038/nsmb.2319 AMP-activated protein kinase (AMPK) has a central role in sensing cellular metabolic levels. Crystal structures of the AMPK core in the presence of AMP or ATP suggest that the third nucleotide-binding site in the γ subunit is important for allosteric regulation of kinase activity. Large-scale mapping of branchpoints in human pre-mRNA transcripts in vivo pp719 - 721 Allison J Taggart, Alec M DeSimone, Janice S Shih, Madeleine E Filloux and William G Fairbrother doi:10.1038/nsmb.2327 The process of pre-mRNA splicing involves connecting two exons while releasing the intron as a transient branched RNA, or as a lariat. Deep-sequencing analysis has enabled the first large-scale identification of branch points in human pre-mRNA transcripts in vivo, onto which the distribution of splicing factor binding was mapped. Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system   pp722 - 724 Chang Shu, Guanghui Yi, Tylan Watts, C Cheng Kao and Pingwei Li doi:10.1038/nsmb.2331 The crystal structures of human STING in the apo and c-di-GMP–bound states, supported by mutagenesis and biochemical data, reveal that c-di-GMP binds to preformed dimeric STING. c-di-GMP prolongs STING phosphorylation in vitro, which may contribute to downstream IFN signaling. These findings aid in understanding the innate immune response to bacterial infection. Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP    pp725 - 727 Guijun Shang, Deyu Zhu, Ning Li, Junbing Zhang, Chunyuan Zhu, Defen Lu, Cuilan Liu, Qian Yu, Yanyu Zhao, Sujuan Xu and Lichuan Gu doi:10.1038/nsmb.2332 STING is an important component of the innate immune system involved in the direct response to the bacterial second messenger c-di-GMP. The structures of human STING in the presence and absence of c-di-GMP show how recognition of c-di-GMP is achieved by dimeric STING, providing a basis for future studies investigating signal transduction mechanisms. The structural basis for the sensing and binding of cyclic di-GMP by STING    pp728 - 730 Yi-He Huang, Xiang-Yu Liu, Xiao-Xia Du, Zheng-Fan Jiang and Xiao-Dong Su doi:10.1038/nsmb.2333 STING is an ER-resident membrane protein that triggers cytokine production upon detection of the bacterial second messenger c-di-GMP. The structures of the cytosolic domain of STING and the complex it forms with c-di-GMP lay the groundwork for understanding STING function. Technical Report Top Visualizing transient protein-folding intermediates by tryptophan-scanning mutagenesis   pp731 - 736 Alexis Vallée-Bélisle and Stephen W Michnick doi:10.1038/nsmb.2322 Tryptophan scanning is now used to characterize transient intermediate states in the folding pathway of a protein. By following the intrinsic fluorescence of tryptophan residues introduced at different solvent-exposed positions of model protein ubiquitin, the authors characterize a late folding intermediate. Top Advertisement Nature Structural & Molecular Biology FOCUS ON TRANSLATIONAL CONTROL Translational control has become a major focus of attention and research activity. The identification of a myriad of new factors and genome-wide targets as well as recent insights into eukaryotic ribosomes, translation initiation and control mechanisms will be discussed in four Reviews and one Perspective by leaders in the field. Access the Focus online: http://www.nature.com/nsmb/focus/translation   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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