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TABLE OF CONTENTS
April 2014 Volume 21, Issue 4
Focus
Editorial
Commentaries
Reviews
News and Views
Articles
Brief Communication
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Focus attached Ubiquitin
Focus issue: April 2014 Volume 21 No 4
Contents
Editorial
Commentaries
Reviews
Sponsor
Editorial
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Focus in c~tinuance Ubiquitin
Essential modifications p289
doi:10.1038/nsmb.2811
Ubiquitin and ubiquitin-like proteins esteem central roles in regulating cellular processes and homeostasis. This Focus examines our brains of the ubiquitination reaction and the mechanisms ~ means of which ubiquitin and related modifications arrogate protein and cellular functions.
Commentaries
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Focus attached Ubiquitin
Ubiquitin sets the timer: impacts without ceasing aging and longevity pp290 – 292
Eva Kevei and Thorsten Hoppe
doi:10.1038/nsmb.2806
Protein homeostasis is necessary for cellular function, organismal growth and viability. Damaged and aggregated proteins are turned over by two major proteolytic routes of the alveolate quality-control pathways: the ubiquitin-proteasome scheme and autophagy. For both these pathways, ubiquitination provides the confession signal for substrate selection. This Commentary discusses in what manner ubiquitin-dependent proteolytic pathways are coordinated through stress- and aging-induced signals.
Focus put ~ Ubiquitin
Plant ubiquitin ligases as signaling hubs pp293 – 296
Nitzan Shabek and Ning Zheng
doi:10.1038/nsmb.2804
The ended decade has witnessed an explosion in the identification of ubiquitin-ligase complexes to the degree that the missing receptors for important unimportant-molecule hormones regulating plant growth and progress to maturity. These breakthroughs were initiated by genetic approaches, by structural analysis providing mechanistic insights into by what means hormone perception and signaling are coupled to protein ubiquitination. Although in that place are still many unknowns, plants regard imparted valuable lessons about the pharmacology of ubiquitin variation.
Focus on Ubiquitin
Ubiquitin in inflammation: the right linkage makes all the difference pp297 – 300
Jacob E Corn and Domagoj Vucic
doi:10.1038/nsmb.2808
The immune arrangement must operate in an effective, prim and safe manner to defend in countervail to diverse pathogens while avoiding attacking the corpse itself and commensal bacteria. Inflammatory pathways mediated through NOD-like, Toll-like, RIG-I-like and tumor-necrosis-factor receptor families are tightly regulated through ubiquitination, especially by Lys63-linked and lineal polyubiquitin chains. Here we discuss the human ubiquitin-mediated inflaming signaling system, emphasizing the interactions and activities whose coordination ensures soon, accurate regulation of inflammatory responses.
Reviews
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Focus attached Ubiquitin
New insights into ubiquitin E3 ligase mechanism pp301 – 307
Christopher E Berndsen and Cynthia Wolberger
doi:10.1038/nsmb.2780
Ubiquitin E3 ligases catalyze the final step of the ubiquitination cascade, promoting the alienation of ubiquitin from the E2 to the substrate mark. Recent structural and biochemical studies take given insights in the catalytic mechanisms of all three E3 ligase classes, as discussed in this Review.
Focus adhering Ubiquitin
Lysine-targeting specificity in ubiquitin and ubiquitin-like variation pathways pp308 – 316
Francesca Mattiroli and Titia K Sixma
doi:10.1038/nsmb.2792
Ubiquitin and ubiquitin-like (UBL) modifications occur primarily on lysine residues of target proteins to work up downstream signals. This Review discusses current judgment of lysine specificity in ubiquitin and UBL targeting, by particular focus on the systems in which a detailed mechanism of modification and downstream signaling has been validated biochemically.
Focus forward Ubiquitin
Two-way communications between ubiquitin-like modifiers and DNA pp317 – 324
Helle D Ulrich
doi:10.1038/nsmb.2805
DNA metabolism is regulated through the ubiquitin and SUMO modifications, limit DNA also influences whether and whenever these modifications occur. This Review describes the correlative interactions between DNA, ubiquitin and SUMO that occur in DNA-associated processes.
Focus attached Ubiquitin
Cleaning up in the endoplasmic reticulum: ubiquitin in charge pp325 – 335
John C Christianson and Yihong Ye
doi:10.1038/nsmb.2793
The endoplasmic reticulum-associated degeneration (ERAD) pathway maintains protein homeostasis in the ER ~ the agency of retrotranslocating unwanted proteins to the cytosol in quest of proteasomal degradation. This Review discusses the whole role of the ubiquitin system in ERAD, highlighting for what cause the two pathways intertwine to make easy transport across the ER membrane.
Focus forward Ubiquitin
Dynamic regulation of macroautophagy by distinctive ubiquitin-like proteins pp336 – 345
Daniel J Klionsky and Brenda A Schulman
doi:10.1038/nsmb.2787
Whereas the proteasome degrades individual proteins modified through ubiquitin chains, autophagy degrades many proteins and organelles en masse. A brace of ubiquitin-like proteins (UBLs), Atg8 and Atg12, order autophagy-mediated degradation in a manner completely distinct from that of ubiquitin in the proteasome pathway, as discussed in this Review.
News and Views
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The JAMM in the proteasome pp346 – 348
Tobias Wauer and David Komander
doi:10.1038/nsmb.2800
Structures of the deubiquitinating enzyme Rpn11 of the proteasomal 19S regulatory molecule reveal its role in hydrolyzing the proximal ubiquitin from a protein that is all over to be degraded.
RPA puts the brakes forward MMEJ pp348 – 349
Mitch McVey
doi:10.1038/nsmb.2802
Microhomology-mediated cessation joining (MMEJ) is a mechanism of DNA double-get ashore-break repair that creates deletions and promotes other types of genome instability. New in vivo and in vitro analyses prove that the heterotrimeric replication protein A (RPA) complicated prevents spontaneous annealing of microhomologies, by that means preventing genome-destabilizing MMEJ.
See in like manner: Article by Deng et al.
Promoter affecting by an alternative σ, one base at a time pp350 – 351
Seth A Darst, Andrey Feklistov and Carol A Gross
doi:10.1038/nsmb.2798
Housekeeping σ factors are indoctrination factors for the bacterial RNA polymerase at greatest number promoters, whereas alternative σs regulate focused responses to specific environmental provisions. Structural and functional analysis of each alternative σ complexed with its connected -10 motif elucidates the mechanism by reason of initiation of strand opening, highlighting two critical properties: why alternative σs, compared to housekeeping σs, acknowledge so few promoters and how their promoter-confession strategy was diversified during evolution.
Structural & Molecular Biology
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Articles
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X-perception crystal structure of voltage-gated proton channel pp352 – 357
Kohei Takeshita, Souhei Sakata, Eiki Yamashita, Yuichiro Fujiwara, Akira Kawanabe et al.
doi:10.1038/nsmb.2783
Structural and functional analysis reveal the resting state of the voltage-gated proton cut furrows in Hv1. Comparison with structures of voltage-sensing domains from other systems, captured in the activated civil community, will aid in understanding the mechanical construction of voltage sensing.
Global effects of the CSR-1 RNA opposition pathway on the transcriptional landscape pp358 – 365
Germano Cecere, Sebastian Hoersch, Sean O’Keeffe, Ravi Sachidanandam and Alla Grishok
doi:10.1038/nsmb.2801
RNAi pathways repress gene expression at the transcriptional and station-transcriptional level. Genome-wide analyses of initial RNA transcripts in nematodes now allude to that the CSR-1 RNAi way helps maintain the directionality of prompt transcription and propagate the distinction betwixt transcriptionally active and silent genomic regions.
Transcriptionally valid chromatin recruits homologous recombination at DNA double-beach breaks pp366 – 374
François Aymard, Beatrix Bugler, Christine K Schmidt, Emmanuelle Guillou, Pierre Caron et al.
doi:10.1038/nsmb.2796
DNA double-get ashore breaks (DSBs) may be repaired one or the other by homologous recombination (HR) or nonhomologous end joining (NHEJ) pathways. A of recent origin high-resolution mapping study of DSBs in human cells shows that trimethylated histone H3 K36, a marker of at work chromatin, targets RAD51 to DSBs inside of transcribed regions to promote preferential HR-mediated repair at transcriptionally efficacious loci.
Structural basis of the proinflammatory signaling complicate mediated by TSLP pp375 – 382
Kenneth Verstraete, Loes covered wagon Schie, Laurens Vyncke, Yehudi Bloch, Jan Tavernier et al.
doi:10.1038/nsmb.2794
Thymic stromal lymphopoietin (TSLP) is a cytokine accurate for the development of chronic tending to inflammation disorders including asthma and atopic dermatitis. The erection of the ternary complex formed through TSLP and its coreceptors TSLPR and the interleukin-7 receptor disclose how TSLP is able to constitute receptor-receptor contacts to facilitate intracellular signaling.
Structural groundwork for pure antagonism of integrin αVβ3 by a high-affinity form of fibronectin pp383 – 388
Johannes F Van Agthoven, Jian-Ping Xiong, José Luis Alonso, Xianliang Rui, Brian D Adair et al.
doi:10.1038/nsmb.2797
Integrins are encouraging targets in the treatment of terms that range from cancer to sagacious coronary syndromes. However, the partial agonism exhibited ~ means of RGD ligand–based drugs can resolve in life-threatening complications. A modern study provides the structural basis concerning pure antagonism by a high-affinity integrin ligand and suggests a road to the design of safer integrin inhibitors.
Ty3 overset transcriptase complexed with an RNA-DNA mule shows structural and functional asymmetry pp389 – 396
Elzbieta Nowak, Jennifer T Miller, Marion K Bona, Justyna Studnicka, Roman H Szczepanowski et al.
doi:10.1038/nsmb.2785
A new study reports the first structure of a retrotransposon mischance transcriptase in complex with its affined polypurine tract RNA-DNA hybrid. In opposition to its retroviral counterparts, Ty3 mischance transcriptase forms an asymmetric homodimer that forms in the air of substrate, with its RNase H and DNA polymerase activities well-suited contributed by separate subunits.
Human immunoglobulin E flexes between acutely bent and extended conformations pp397 – 404
Nyssa Drinkwater, Benjamin P Cossins, Anthony H Keeble, Michael Wright, Katharine Cain et al.
doi:10.1038/nsmb.2795
IgE molecules peer with the FcεRIα receptor in ~y acutely bent conformation where the Cε2 domains cot over the Cε3-Cε4 domains. A commencing study demonstrates that IgE can have life in an extended conformation with a Cε2 dominion capable of flipping from side to espouse a cause, suggesting a level of structural compliance that could functionally impact allergen recognition.
RPA antagonizes microhomology-mediated repair of DNA double-shore breaks pp405 – 412
Sarah K Deng, Bryan Gibb, Mariana Justino de Almeida, Eric C Greene and Lorraine S Symington
doi:10.1038/nsmb.2786
Resection of DNA double strand–batter ends generates single strands that have power to spontaneously anneal to undergo mutagenic microhomology-mediated cessation joining (MMEJ). A combination of genetic and biophysical assays very lately shows that replication protein A (RPA) thwarts be cast away annealing by binding to the resected ends to forward Rad51 filament assembly and error-prodigal repair by homologous recombination.
See likewise: News and Views by McVey
Mechanism of IRSp53 disallowance and combinatorial activation by Cdc42 and downstream effectors pp413 – 422
David J Kast, Changsong Yang, Andrea Disanza, Malgorzata Boczkowska, Yadaiah Madasu et al.
doi:10.1038/nsmb.2781
IRSp53 is a BAR-territory protein under the control of Rho household GTPases and has crucial roles in processes such as cell motility and tumor invasiveness. In a commencing study, IRSp53 is shown to have ~ing autoinhibited and is synergistically activated ~ dint of. the combinatorial action of Cdc42 and the tumor-promoting factor Eps8.
Brief Communication
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The retrovirus HERVH is a lengthy noncoding RNA required for human embryonic branch cell identity pp423 – 425
Xinyi Lu, Friedrich Sachs, LeeAnn Ramsay, Pierre-Étienne Jacques, Jonathan Göke et al.
doi:10.1038/nsmb.2799
Human endogenous retrovirus subfamily H (HERVH) is a class of transposable elements expressed preferentially in human embryonic stock cells (hESCs). A new study at present shows that the long terminal repeats of HERVH function as enhancers and that HERVH is a nuclear to a great extent noncoding RNA required to maintain hESC identity.
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