Nature Structural & Molecular Biology Contents: February 2012 Volume #19 pp 129 - 264

Advertisement One-STrEP-tag the high affinity Strep-tag II One-STrEP-tag combines high affinity with high specifity, therefore allowing isolation of highly pure and functional proteins even from batch. Mild elution conditions preserve protein complexes and protein interactions... Click here for application examples TABLE OF CONTENTS February 2012 Volume 19, Issue 2 News and Views Research Highlights Articles Brief Communication Corrigendum Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Reprint Collection: microRNAs This collection of recent papers from Nature and other NPG journals highlights developments in microRNA biology and effects on gene regulation. Access the reprint collection free online for six months. Produced with support from: Regulus Therapeutics Inc.   News and Views Top It takes two to transport, or is it one? pp129 - 130 Hyun-Ho Lim and Christopher Miller doi:10.1038/nsmb.2239 The proteins that 'pump' neurotransmitters into neurons, clearing the synapse after a nerve impulse, are central players in coherent brain function and are targets of many psychotropic drugs. Two groups now endeavor to resolve a fundamental controversy about how these proteins work. The results shed new light on the controversy but do not end it. Full Text | PDF See also: Article by Quick et al. | Article by Wang et al. Cbl exposes its RING finger pp131 - 133 Stephen C Kales, Philip E Ryan and Stanley Lipkowitz doi:10.1038/nsmb.2241 The Cbl family of RING finger ubiquitin ligases regulates signaling in many systems. Two new studies provide a structural basis for how phosphorylation of a specific tyrosine in the Cbl proteins enhances their ubiquitin ligase activity, giving insight into how ubiquitination by Cbl proteins is restricted to specific substrates. Full Text | PDF See also: Article by Dou et al. A team effort blocks the ribosome in its tracks pp133 - 134 Amy E Pasquinelli doi:10.1038/nsmb.2236 A complex of PUF (named after founding members Pumilio and Fem-3 binding factor) and Argonaute proteins can stall translation elongation on bound mRNAs by interacting with eEF1A and inhibiting its GTPase activity. Full Text | PDF See also: Article by Friend et al. Research Highlights Swift, strandwise translocation | Adaptation by RNA editing | Tumor-suppressive Smurf | Intrinsic regulation Structural & Molecular Biology JOBS of the week Research Technologist - Structural Biology St. Jude Children's Research Hospital International PhD Program Molecular Cell Biology Max Delbrück Center for Molecular Medicine Postdoc offer at the NSTRUCT Image Processing Center in Microscopy, CNB-CSIC, Madrid cnb-csic Research Lab Specialist St. Jude Children's Research Hospital More Science jobs from Structural & Molecular Biology EVENT Mutations, Malignancy and Memory - Antibodies and Immunity (C6) 18th - 22nd March 2012 MA, US More science events from Articles Top Symmetric dimethylation of H3R2 is a newly identified histone mark that supports euchromatin maintenance pp136 - 144 Valentina Migliori, Julius Müller, Sameer Phalke, Diana Low, Marco Bezzi, Wei Chuen Mok, Sanjeeb Kumar Sahu, Jayantha Gunaratne, Paola Capasso, Christian Bassi, Valentina Cecatiello, Ario De Marco, Walter Blackstock, Vladimir Kuznetsov, Bruno Amati, Marina Mapelli and Ernesto Guccione doi:10.1038/nsmb.2209 Although the asymmetric dimethylation of histone H3R2 acts as a repressive mark, new studies reveal that symmetrically dimethylated H3R2 (H3R2me2s) is a functional histone mark in vivo. The RBBP7 co-repressor is excluded from binding H3R2me2s in favor of the coactivator WDR5, which poises euchromatic genes for transcription activation upon cell-cycle exit and differentiation. Abstract | Full Text | PDF The N domain of Argonaute drives duplex unwinding during RISC assembly pp145 - 151 Pieter Bas Kwak and Yukihide Tomari doi:10.1038/nsmb.2232 Small noncoding RNAs function together with Argonaute (Ago) proteins as part of RNA-induced silencing complexes (RISCs). New biochemical analyses have identified the N domain of human AGO2 as the initiator of small duplex RNA unwinding during RISC assembly, which is required for both slicer-dependent and slicer-independent unwinding mechanisms. Abstract | Full Text | PDF Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ pp152 - 157 Hélène Malet, Flavia Canellas, Justyna Sawa, Jun Yan, Konstantinos Thalassinos, Michael Ehrmann, Tim Clausen and Helen R Saibil doi:10.1038/nsmb.2210 HtrA proteins have chaperone and protease activities, but how they bind and fold their substrates is poorly understood. New cryo-EM analyses of a protease-defective bacterial DegQ mutant in complex with several different substrates provide a structural model of HtrA proteins in their chaperone mode. Abstract | Full Text | PDF Structure of a KirBac potassium channel with an open bundle crossing indicates a mechanism of channel gating pp158 - 163 Vassiliy N Bavro, Rita De Zorzi, Matthias R Schmidt, João R C Muniz, Lejla Zubcevic, Mark S P Sansom, Catherine Vénien-Bryan and Stephen J Tucker doi:10.1038/nsmb.2208 KirBac channels are the bacterial homologs of mammalian inwardly rectifying potassium (Kir) channels. All available structures are closed at the helix bundle crossing, but the crystal structure of an open-state KirBac channel now indicates how opening of the primary activation gate may be physically coupled to a rotational twist in the cytoplasmic domain. Abstract | Full Text | PDF Regulation of Rev1 by the Fanconi anemia core complex pp164 - 170 Hyungjin Kim, Kailin Yang, Donniphat Dejsuphong and Alan D D'Andrea doi:10.1038/nsmb.2222 The Fanconi anemia pathway is involved in the repair of DNA interstrand cross-links, but it is also involved in regulation of translesion synthesis (TLS). The protein FAAP20 is now identified as a subunit of the Fanconi anemia core complex. FAAP20 interacts with TLS DNA polymerase Rev1, stabilizing Rev1's association with PCNA and promoting DNA damage bypass. Abstract | Full Text | PDF Phosphorylation-dependent activity of the deubiquitinase DUBA pp171 - 175 Oscar W Huang, Xiaolei Ma, JianPing Yin, Jeremy Flinders, Till Maurer, Nobuhiko Kayagaki, Qui Phung, Ivan Bosanac, David Arnott, Vishva M Dixit, Sarah G Hymowitz, Melissa A Starovasnik and Andrea G Cochran doi:10.1038/nsmb.2206 Protease phosphorylation has been reported to affect many signaling pathways connected to proteolytic activity, but the underlying mechanisms have not been clearly elucidated. Structural and biochemical analyses of the deubiquitinase DUBA reveal that phosphorylation is necessary for productive ubiquitin substrate recognition and for enzyme activity. Abstract | Full Text | PDF A conserved PUF–Ago–eEF1A complex attenuates translation elongation pp176 - 183 Kyle Friend, Zachary T Campbell, Amy Cooke, Peggy Kroll-Conner, Marvin P Wickens and Judith Kimble doi:10.1038/nsmb.2214 PUF (Pumilio/FBF) RNA-binding proteins and Argonaute (Ago) miRNA-binding proteins regulate mRNAs post-transcriptionally, each acting through similar yet distinct mechanisms. New genetic and biochemical analyses demonstrate that PUF and Ago proteins also function together in complex with elongation factor eEF1A to repress translation elongation. Abstract | Full Text | PDF See also: News and Views by Pasquinelli Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl  pp184 - 192 Hao Dou, Lori Buetow, Andreas Hock, Gary J Sibbet, Karen H Vousden and Danny T Huang doi:10.1038/nsmb.2231 Cbl RING ubiquitin ligases regulate receptor tyrosine kinase signal transduction and are in turn regulated by phosphorylation in their linker helix regions. Structural and biochemical analysis now shows that phosphorylation of c-Cbl leads to the release of an autoinhibited conformation, enhancing E2 binding and promoting ubiquitination activity. Abstract | Full Text | PDF See also: News and Views by Kales et al. Dynein achieves processive motion using both stochastic and coordinated stepping pp193 - 200 Weihong Qiu, Nathan D Derr, Brian S Goodman, Elizabeth Villa, David Wu, William Shih and Samara L Reck-Peterson doi:10.1038/nsmb.2205 The processivity of myosins and kinesins has been well studied, but how the dynein homodimer achieves continuous motion is unknown. Two-dimensional analysis of labeled, DNA-dimerized dynein demonstrates that dynein has an unusual stepping pattern and can alternate between stochastic- and tension-based stepping to achieve processivity. Abstract | Full Text | PDF The E3 ligase RNF8 regulates KU80 removal and NHEJ repair pp201 - 206 Lin Feng and Junjie Chen doi:10.1038/nsmb.2211 RNF8 and RNF168 are E3 ligases that promote the ubiquitination of histones at sites of double-strand breaks. Now RNF8 is shown to form mainly Lys48-linked ubiquitin chains and to modify KU80 bound to DNA breaks, promoting its removal and completion of DNA repair by NHEJ. Abstract | Full Text | PDF Experimental conditions can obscure the second high-affinity site in LeuT pp207 - 211 Matthias Quick, Lei Shi, Britta Zehnpfennig, Harel Weinstein and Jonathan A Javitch doi:10.1038/nsmb.2197 Crystal structures of the bacterial LeuT Na+-substrate symporter have revealed one substrate molecule in an occluded, centrally located binding site, whereas subsequent studies identified a putative second substrate binding site. Now additional binding analyses demonstrate that the second substrate binding site can be obscured during the preparation of detergent-solubilized LeuT for crystallography, explaining the apparent discrepancy in the reported stoichiometry. Abstract | Full Text | PDF See also: News and Views by Lim & Miller Structures of LeuT in bicelles define conformation and substrate binding in a membrane-like context pp212 - 219 Hui Wang, Johannes Elferich and Eric Gouaux doi:10.1038/nsmb.2215 Recent studies have called into question the extent to which crystal structures of LeuT solubilized in β-OG detergent micelles reflect functionally relevant states. Now crystal structures of LeuT in lipid bicelles—a more native membrane-like context—show LeuT–substrate complexes nearly identical to the previously reported ones, with a single substrate molecule in the primary binding site. Abstract | Full Text | PDF See also: News and Views by Lim & Miller The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation pp220 - 228 Olga Anczuków, Avi Z Rosenberg, Martin Akerman, Shipra Das, Lixing Zhan, Rotem Karni, Senthil K Muthuswamy and Adrian R Krainer doi:10.1038/nsmb.2207 The splicing factor SRSF1 is an oncoprotein that is upregulated in human tumors, including breast cancer tumors. New in vitro and in vivo analyses reveal SRSF1's ability to transform human mammary epithelial cells and promote mammary gland tumorigenesis in a mouse model by regulating apoptosis and proliferation and cooperating with Myc while also uncovering potential downstream therapeutic targets. Abstract | Full Text | PDF Molecular basis for RNA polymerization by Qβ replicase pp229 - 237 Daijiro Takeshita and Kozo Tomita doi:10.1038/nsmb.2204 The core Qβ replicase is comprised of Qβ virus-encoded RNA-dependent polymerase and bacterial host–derived EF-Tu and EF-Ts, but the functions of these translation factors in RNA polymerization have been unclear. Structural analysis of Qβ replicase during polymerization reveals that EF-Tu functions as a modulator to separate the growing RNA strand from the template, ensuring processivity of the complex. Abstract | Full Text | PDF Crystal structure of quinol-dependent nitric oxide reductase from Geobacillus stearothermophilus  pp238 - 245 Yushi Matsumoto, Takehiko Tosha, Andrei V Pisliakov, Tomoya Hino, Hiroshi Sugimoto, Shingo Nagano, Yuji Sugita and Yoshitsugu Shiro doi:10.1038/nsmb.2213 Quinol-dependent nitric oxide reductase (qNOR) catalyzes the reduction of nitric oxide, which is emitted by bacteria, to produce nitrous oxide—an ozone-depleting gas and potent greenhouse gas. The crystal structure of qNOR from Geobacillus stearothermophilus allows a structural comparison with other respiratory enzymes, revealing functionally important similarities and differences between anaerobic and aerobic respiration. Abstract | Full Text | PDF Mre11 regulates CtIP-dependent double-strand break repair by interaction with CDK2 pp246 - 252 Jeffrey Buis, Trina Stoneham, Elizabeth Spehalski and David O Ferguson doi:10.1038/nsmb.2212 Eukaryotic cells choose the pathway to repair DNA double-strand breaks according to the cell-cycle phase, with homologous recombination preferred during S and G2 phases. Now the direct interaction between CDK2 and the C-terminus of Mre11 is revealed and shown to be important for phosphorylation of CtIP. Abstract | Full Text | PDF HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism pp253 - 259 Kalyan Das, Sergio E Martinez, Joseph D Bauman and Eddy Arnold doi:10.1038/nsmb.2223 Non-nucleoside inhibitors (NNRTIs) against HIV-1 reverse transcriptase (RT) are used clinically, but the mechanism by which they interfere with RT's activity is still unclear. The crystal structure of a ternary complex composed of RT, primer-template DNA and NNRTI nevirapine now reveals that binding of the drug shifts the primer 3′ end from the active site, preventing nucleotide incorporation. Abstract | Full Text | PDF Brief Communication Top Chromodomains read the arginine code of post-translational targeting pp260 - 263 Iris Holdermann, N Helge Meyer, Adam Round, Klemens Wild, Michael Sattler and Irmgard Sinning doi:10.1038/nsmb.2196 Nuclear chromodomain-containing proteins read the epigenetic code by recognizing methylated lysine residues in histone tails. Structural analysis of the cytoplasmic chloroplast signal recognition particle subunit cpSRP34 in complex with the cpSRP54 subunit C-terminal tail comprising an arginine-rich motif reveals that a twinned aromatic cage reads two neighboring nonmethylated arginine residues and adapts chromodomains to a function outside the nucleus. First paragraph | Full Text | PDF Corrigendum Top A single amino acid residue can determine the sensitivity of SERCAs to artemisinins p264 Anne-Catrin Uhlemann, Angus Cameron, Ursula Eckstein-Ludwig, Jorge Fischbarg, Pavel Iserovich, Felipe A Zuniga, Malcolm East, Anthony Lee, Leo Brady, Richard K Haynes and Sanjeev Krishna doi:10.1038/nsmb0212-264 Full Text | PDF Top Advertisement Nature Chemical Biology Free Poster on Human protein methyltransferases Nature Chemical Biology presents a poster highlighting the human protein methyltransferase families, the small molecules known to target them and the prospects for PMT-focused drug development. Download the Poster today by visiting: www.nature.com/nchembio/poster/hpm Poster sponsored by:   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. 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