Nature Structural & Molecular Biology Contents: December 2012 Volume #19 pp 1203 - 1377

TABLE OF CONTENTS December 2012 Volume 19, Issue 12 Commentary News and Views Obituary Review Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement The Encyclopedia of DNA Elements 30 papers published simultaneously in Nature, Genome Research and Genome Biology. Access videos, Features and the collected research papers, and explore the thematic threads that run through them via the Nature ENCODE explorer or the NatureENCODE app. Request a free sample copy. Produced with support from Illumina   Commentary Top Data management challenges in three-dimensional EM   pp1203 - 1207 Ardan Patwardhan, Jose-Maria Carazo, Bridget Carragher, Richard Henderson, J Bernard Heymann, Emma Hill, Grant J Jensen, Ingvar Lagerstedt, Catherine L Lawson, Steven J Ludtke, David Mastronarde, William J Moore, Alan Roseman, Peter Rosenthal, Carlos-Oscar S Sorzano, Eduardo Sanz-Garcia, Sjors H W Scheres, Sriram Subramaniam, John Westbrook, Martyn Winn, Jason R Swedlow and Gerard J Kleywegt doi:10.1038/nsmb.2426 This report describes the outcomes of the Data Management Challenges in 3D Electron Microscopy workshop. Key topics discussed include data models, validation and raw-data archiving. The meeting participants agreed that the EMDataBank should take the lead in addressing these issues, and concrete action points were agreed upon that will have a substantial impact on the accessibility of three-dimensional EM data in biology and medicine. News and Views Top Ancient, giant riboswitches at atomic resolution   pp1208 - 1209 Ronald R Breaker doi:10.1038/nsmb.2453 Two recent reports on the structures of cobalamin riboswitches uncover amazing details on how a ubiquitous riboswitch class selectively grips a large and ancient coenzyme, revealing that some variants in this class have evolved to detect a different metabolite target. Intimate liaison with SR proteins brings exon junction complexes to unexpected places   pp1209 - 1211 Oliver Muhlemann doi:10.1038/nsmb.2454 Exon junction complexes (EJCs) are deposited on mRNAs during splicing and are key regulators of the post-transcriptional fate of messenger ribonucleoprotein particles (mRNPs). Two recent papers reporting on the transcriptome-wide mapping of EJC-binding sites in human cells reveal an unexpected heterogeneity of EJC distribution on mRNAs and a tight network of EJC-SR protein interactions contributing to the formation of a higher-order, compacted mRNP structure. Tyrosyl DNA phosphodiesterase 2, an enzyme fit for purpose   pp1212 - 1213 Keith W. Caldecott doi:10.1038/nsmb.2455 Three structures were recently reported for tyrosyl DNA phosphodiesterase 2 (Tdp2), a protein that protects the metazoan genome from shredding following abortive topoisomerase activity. The physiological significance of these findings is discussed here. See also: Article by Schellenberg et al. | Article by Shi et al. H3K36me3 key to Polycomb-mediated gene silencing in lineage specification   pp1214 - 1215 Jumana AlHaj Abed and Richard S. Jones doi:10.1038/nsmb.2458 A newly uncovered activity of a family of Polycomb-group proteins provides insight into the mechanisms by which active genes become repressed during the transition from pluripotency to restricted cell fates as stem cells undergo lineage specification. See also: Article by Ballaré et al. | Article by Musselman et al. | Article by Brien et al. Obituary Louise N. Johnson 1940-2012   pp1216 - 1217 David Barford and David I. Stuart doi:10.1038/nsmb.2464 Structural & Molecular Biology JOBS of the week 4-year PhD Interdisciplinary Programme in Structural, Computational and Chemical Biology at UCL / Birkbeck / NIMR ISMB (Birkbeck/UCL) Research Investigators - Structural Biology Novartis Institutes for BioMedical Research (NIBR) Postdoctoral Position in Structural Biology at OIST Okinawa Institute of Science and Technology (OIST) Assistant Professor of Structural Biology / Biophysics ETH Zurich Assistant Professor of Structural Biology / Biophysics ETH 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 Perceiving the epigenetic landscape through histone readers   pp1218 - 1227 Catherine A Musselman, Marie-Eve Lalonde, Jacques Côté and Tatiana G Kutateladze doi:10.1038/nsmb.2436 Histone post-translational modifications (PTMs) can directly influence histone-DNA and histone-histone interactions, or they can be targeted by protein effectors, or histone readers. This Review outlines known readers of histone PTMs, details their mechanism of action and the functional significance of histone PTM recognition and discusses cross-talk between protein effectors and consequences of the combinatorial readout of PTMs. Articles Top Cryo-EM structures of Arx1 and maturation factors Rei1 and Jjj1 bound to the 60S ribosomal subunit   pp1228 - 1233 Basil J Greber, Daniel Boehringer, Christian Montellese and Nenad Ban doi:10.1038/nsmb.2425 Cryo-EM studies of the 60S ribosomal subunit reconstituted with biogenesis factor Arx1 and Rei1 and Jji1 suggest that, in addition to its role during pre-60S nuclear export, Arx1 shields the polypeptide tunnel-exit region and inhibits the premature association of nascent chain–processing factors, whereas Rei1 and Jjj1, which have been implicated in Arx1 recycling, may function in Arx1 release from the tunnel exit. Structure of the pre-60S ribosomal subunit with nuclear export factor Arx1 bound at the exit tunnel   pp1234 - 1241 Bettina Bradatsch, Christoph Leidig, Sander Granneman, Marén Gnädig, David Tollervey, Bettina Böttcher, Roland Beckmann and Ed Hurt doi:10.1038/nsmb.2438 Preribosomal particles need to be exported from the nucleus, but their architecture and composition have been unknown. Cryo-EM analysis of pre-60S particles bound to the nuclear export factor Arx1 provides the first structural glance at the immature 60S particle, and the position of Arx1 near the exit tunnel suggests that it may restrict access of factors active during translation. Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7–Atg3 and Atg7–Atg10 structures   pp1242 - 1249 Stephen E Kaiser, Kai Mao, Asad M Taherbhoy, Shanshan Yu, Jennifer L Olszewski, David M Duda, Igor Kurinov, Alan Deng, Timothy D Fenn, Daniel J Klionsky and Brenda A Schulman doi:10.1038/nsmb.2415 An early step in the autophagy process is the conjugation of the ubiquitin-like proteins (UBLs) Atg8 and Atg12 to their targets. Structural and functional experiments reveal how the autophagy E1 Atg7 uses a trans mechanism to catalyze the charging of the autophagy UBLs onto their respective carrier E2 proteins, Atg3 and Atg10. Noncanonical recognition and UBL loading of distinct E2s by autophagy-essential Atg7    pp1250 - 1256 Masaya Yamaguchi, Kazuaki Matoba, Ryoko Sawada, Yuko Fujioka, Hitoshi Nakatogawa, Hayashi Yamamoto, Yoshihiro Kobashigawa, Hisashi Hoshida, Rinji Akada, Yoshinori Ohsumi, Nobuo N Noda and Fuyuhiko Inagaki doi:10.1038/nsmb.2451 The enzymes involved in autophagy-related UBL conjugation bear only passing resemblance to their counterparts in the better-known UBL conjugation pathways. New structural work provides insight into the mechanism by which the UBL proteins Atg8 and Atg12 are correctly charged by a single activating enzyme, Atg7, then transferred onto their cognate E2 proteins, Atg3 and Atg10, respectively. Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity   pp1257 - 1265 Cecilia Ballaré, Martin Lange, Audrone Lapinaite, Gloria Mas Martin, Lluis Morey, Gloria Pascual, Robert Liefke, Bernd Simon, Yang Shi, Or Gozani, Teresa Carlomagno, Salvador Aznar Benitah and Luciano Di Croce doi:10.1038/nsmb.2434 Methylation of H3K27 by Polycomb repressive complex 2 (PRC2) is essential for gene regulation. A new study provides structural evidence for the recognition of di- and trimethylated H3K36 by the Tudor domain of PRC2 subunit Phf19 as well as functional data suggesting that recognition of di- or trimethylated Phf19–H3K36 is required for regulating PRC2 activity and for full repression of selected PRC2 targets in embryonic stem cells. See also: News and Views by AlHaj Abed & Jones Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1    pp1266 - 1272 Catherine A Musselman, Nikita Avvakumov, Reiko Watanabe, Christopher G Abraham, Marie-Eve Lalonde, Zehui Hong, Christopher Allen, Siddhartha Roy, James K Nuñez, Jac Nickoloff, Caroline A Kulesza, Akira Yasui, Jacques Côté and Tatiana G Kutateladze doi:10.1038/nsmb.2435 The human Polycomb-like protein PHF1 has been implicated in transcription-regulatory and DNA damage repair pathways. A new study demonstrates that the Tudor domain of PHF1 binds histone H3K36me3 with high specificity and affinity, that Tudor-H3K36me3 interaction inhibits Polycomb repressive complex 2-mediated H3K27 methylation and that PHF1 accumulates at DNA damage sites in a Tudor-dependent manner. See also: News and Views by AlHaj Abed & Jones Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation   pp1273 - 1281 Gerard L Brien, Guillermo Gambero, David J O'Connell, Emilia Jerman, Siobhán A Turner, Chris M Egan, Eiseart J Dunne, Maike C Jurgens, Kieran Wynne, Lianhua Piao, Amanda J Lohan, Neil Ferguson, Xiaobing Shi, Krishna M Sinha, Brendan J Loftus, Gerard Cagney and Adrian P Bracken doi:10.1038/nsmb.2449 How Polycomb repressive complex 2 (PRC2) is recruited to active chromatin to mediate transcriptional silencing during lineage specification in metazoans has been unclear. New findings now show that PRC2 component PHF19, which associates with the H3K36me3 demethylase NO66, binds the active chromatin mark H3K36me3 through its Tudor domain, leading to PRC2-mediated H3K27 trimethylation, loss of H3K36me3 and transcriptional silencing. See also: News and Views by AlHaj Abed & Jones Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis   pp1282 - 1286 Giuseppe Nicastro, María Flor García-Mayoral, David Hollingworth, Geoff Kelly, Stephen R Martin, Paola Briata, Roberto Gherzi and Andres Ramos doi:10.1038/nsmb.2427 The protein KSRP binds to precursors of let-7 miRNA and promotes their processing to the mature form. The molecular basis for KSRP's specificity for pre-let-7 is now examined by using NMR spectroscopy and biochemistry, which reveals that the third KH domain of KSRP recognizes a G-rich sequence in the pre-let-7 terminal loop in a noncanonical manner. Structure of the variant histone H3.3–H4 heterodimer in complex with its chaperone DAXX    pp1287 - 1292 Chao-Pei Liu, Chaoyang Xiong, Mingzhu Wang, Zhouliang Yu, Na Yang, Ping Chen, Zhiguo Zhang, Guohong Li and Rui-Ming Xu doi:10.1038/nsmb.2439 The histone variant H3.3 is deposited onto pericentric and telomeric heterochromatin by the histone chaperone DAXX. How DAXX selectively recognizes H3.3 over the canonical H3.1 is now revealed by the crystal structure of DAXX in complex with H3.3–H4, along with biochemical and cellular analyses. Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex   pp1293 - 1299 Bert J C Janssen, Tomas Malinauskas, Greg A Weir, M Zameel Cader, Christian Siebold and E Yvonne Jones doi:10.1038/nsmb.2416 Semaphorin-plexin cell-cell signaling is important in tissue development, with roles in axon guidance, immunity and cancer. The structure of the complex formed between semaphorin-3, plexin-A and their co-receptor neuropilin, combined with mutagenesis, reveals how neuropilin contributes to stabilizing the signaling complex. The binding of Varp to VAMP7 traps VAMP7 in a closed, fusogenically inactive conformation   pp1300 - 1309 Ingmar B Schäfer, Geoffrey G Hesketh, Nicholas A Bright, Sally R Gray, Paul R Pryor, Philip R Evans, J Paul Luzio and David J Owen doi:10.1038/nsmb.2414 VAMP7 is a SNARE protein involved in the fusion of endosomes and lysosomes with various cellular membranes. The longin domain of VAMP7 forms autoinhibitory interactions that prevent VAMP7 SNARE assembly. New structural and functional data reveal how the regulatory protein Varp, a known VAMP7 binding partner, kinetically inhibits SNARE complex formation. X-ray structure of the Yersinia pestis heme transporter HmuUV   pp1310 - 1315 Jae-Sung Woo, Antra Zeltina, Birke A Goetz and Kaspar P Locher doi:10.1038/nsmb.2417 Gram-negative bacteria use heme import systems to sequester heme from their environment. The structure of the ABC transporter HmuUV, the heme importer from Yersinia pestis, in the nucleotide-free, apo state was determined, revealing an outward-facing conformation for the transporter. ATPase-dependent role of the atypical kinase Rio2 on the evolving pre-40S ribosomal subunit   pp1316 - 1323 Sébastien Ferreira-Cerca, Vatsala Sagar, Thorsten Schäfer, Momar Diop, Anne-Maria Wesseling, Haiyun Lu, Eileen Chai, Ed Hurt and Nicole LaRonde-LeBlanc doi:10.1038/nsmb.2403 Rio2 is an atypical protein kinase required for pre-40S subunit maturation. The crystal structure of eukaryotic Rio2 with bound ATP and Mg2+ reveals an unusual phosphoaspartate intermediate typically observed in P-type ATPases. Rio2 has in vitro ATPase activity, and its catalytic activity stimulates its own dissociation from the ribosome, which is required for pre-40S maturation. A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5′ exonucleolytic degradation   pp1324 - 1331 Joerg E Braun, Vincent Truffault, Andreas Boland, Eric Huntzinger, Chung-Te Chang, Gabrielle Haas, Oliver Weichenrieder, Murray Coles and Elisa Izaurralde doi:10.1038/nsmb.2413 The removal of the mRNA 5′ cap structure by the decapping enzyme DCP2 leads to rapid 5′→3′ mRNA degradation by XRN1, suggesting that the two processes are coordinated. Biochemical and structural analyses now reveal a molecular basis for this coupling by showing that XRN1 directly interacts with the decapping activators EDC4 and DCP1 in human and Drosophila melanogaster cells, respectively. Dynamic switch of the signal recognition particle from scanning to targeting   pp1332 - 1337 Wolf Holtkamp, Sejeong Lee, Thomas Bornemann, Tamara Senyushkina, Marina V Rodnina and Wolfgang Wintermeyer doi:10.1038/nsmb.2421 Ribosomes that synthesize membrane proteins are targeted to the protein-conducting channel in the membrane via the signal recognition particle (SRP) pathway. Kinetic analyses now demonstrate that SRP scans ribosomes while undergoing dynamic fluctuations until it encounters a nascent peptide in the exit tunnel and binds the hydrophobic signal-anchor sequence, which stabilizes SRP and switches it into targeting mode. A tightly regulated molecular toggle controls AAA+ disaggregase   pp1338 - 1346 Yuki Oguchi, Eva Kummer, Fabian Seyffer, Mykhaylo Berynskyy, Benjamin Anstett, Regina Zahn, Rebecca C Wade, Axel Mogk and Bernd Bukau doi:10.1038/nsmb.2441 In the E. coli Hsp100/Hsp70 system, the M domain of ClpB is essential for ClpB cooperation with DnaK and DnaJ and for protein disaggregation, but its function was largely unknown. New biochemical and biophysical data now indicate that the M domain acts as a molecular toggle that reversibly interacts with the AAA-1 domain of ClpB to regulate ATP hydrolysis and protein disaggregation activities. Also in this issue, Seyffer et al. show how DnaK interactions with M domain further enhance ClpB activity. Hsp70 proteins bind Hsp100 regulatory M domains to activate AAA+ disaggregase at aggregate surfaces   pp1347 - 1355 Fabian Seyffer, Eva Kummer, Yuki Oguchi, Juliane Winkler, Mohit Kumar, Regina Zahn, Victor Sourjik, Bernd Bukau and Axel Mogk doi:10.1038/nsmb.2442 DnaK targets protein aggregates to ClpB. New data show that DnaK also activates ClpB in a species-specific manner through direct interactions with the M domain of ClpB, stabilizing a derepressed state that increases the ATP hydrolysis and protein disaggregation activities of the chaperone. Also in this issue, Oguchi et al. show how the M domain of ClpB acts as a reversible toggle to regulate these activities. Structure of the vacuolar-type ATPase from Saccharomyces cerevisiae at 11-Å resolution   pp1356 - 1362 Samir Benlekbir, Stephanie A Bueler and John L Rubinstein doi:10.1038/nsmb.2422 Vacuolar-type ATPases (V-type ATPases) are large integral membrane protein complexes. Their activity acidifies intracellular compartments, and they are regulated by the dissociation of the complex's V1 and VO regions. The cryo-EM reconstruction of the yeast V-type ATPase suggests how structural rearrangements triggered by dissociation of V1 leads to inhibition of activity. Mechanism of repair of 5′-topoisomerase II–DNA adducts by mammalian tyrosyl-DNA phosphodiesterase 2    pp1363 - 1371 Matthew J Schellenberg, C Denise Appel, Sanjay Adhikari, Patrick D Robertson, Dale A Ramsden and R Scott Williams doi:10.1038/nsmb.2418 Tyrosyl-DNA phosphodiesterase 2 (Tdp2) processes DNA termini with a 5′-phosphotyrosyl–linked topoisomerase II adduct, such as those stabilized by chemotherapeutic drugs anthracyclines and etoposides, by direct reversal of the 5′-phosphotyrosyl linkage. Now crystal structures of mouse Tdp2–DNA complexes, along with mutagenesis and functional analyses, reveal how Tdp2 recognizes and reverses such adduction. See also: News and Views by Caldecott Structural basis for recognition of 5′-phosphotyrosine adducts by Tdp2    pp1372 - 1377 Ke Shi, Kayo Kurahashi, Rui Gao, Susan E Tsutakawa, John A Tainer, Yves Pommier and Hideki Aihara doi:10.1038/nsmb.2423 DNA-repair enzyme Tdp2 hydrolyzes the 5'-phosphotyrosine bond formed by topoisomerases and is associated with resistance to anticancer drugs that trap such complexes. The crystal structures of zebrafish Tdp2 bound to DNA offer insight into substrate recognition. In addition, the crystal structure of nematode Tdp2 suggests a potential mechanism for autoregulation. See also: News and Views by Caldecott 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

You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/myaccount (You will need to log in to be recognised as a nature.com registrant) For further technical assistance, please contact our registration department For print subscription enquiries, please contact our subscription department For other enquiries, please contact our customer feedback department Nature Publishing Group | 75 Varick Street, 9th Floor | New York | NY 10013-1917 | USA Nature Publishing Group's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at Brunel Road, Houndmills, Basingstoke, Hampshire RG21 6XS. © 2012 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.