TABLE OF CONTENTS |
May 2014 Volume 10, Issue 5 |
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Nature Structural & Molecular Biology FOCUS ON UBIQUITIN
Ubiquitin and ubiquitin-like proteins have central roles in regulating cellular processes and homeostasis. This Focus examines our understanding of the ubiquitination reaction and the mechanisms by which ubiquitin and related modifications affect key cellular functions.
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Commentary | Top |
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Engineering synergy in biotechnology pp319 - 322 Jens Nielsen, Martin Fussenegger, Jay Keasling, Sang Yup Lee, James C Liao et al. doi:10.1038/nchembio.1519 Biotechnology is a central focus in efforts to provide sustainable solutions for the provision of fuels, chemicals and materials. On the basis of a recent open discussion, we summarize the development of this field, highlighting the distinct but complementary approaches provided by metabolic engineering and synthetic biology for the creation of efficient cell factories to convert biomass and other feedstocks to desired chemicals.
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Research Highlights | Top |
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Metal regulation: Iron clad delivery | Immunology: Interfering with Interferon | Plant innate immunity: Tussling over tyrosine | Peptides: A synthetic step change | Cell biology: Just the two of us | Apoptosis: A channel off-target | Natural products: A painful discovery | Kinase regulation: Switching GSK3 off
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News and Views | Top |
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Perspective | Top |
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Rethinking biological activation of methane and conversion to liquid fuels pp331 - 339 Chad A Haynes and Ramon Gonzalez doi:10.1038/nchembio.1509 Methane is an energy resource that is currently being wasted through emissions, venting and flaring during petroleum extraction. Recent discoveries regarding the basis of enzyme function and microbial metabolism provide the foundation for new thinking about how to reclaim this resource through bioconversion.
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Brief Communication | Top |
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Structural basis for hijacking siderophore receptors by antimicrobial lasso peptides pp340 - 342 Indran Mathavan, Séverine Zirah, Shahid Mehmood, Hassanul G Choudhury, Christophe Goulard et al. doi:10.1038/nchembio.1499

Lasso peptides are antimicrobial bacterial peptides that hijack outer membrane siderophores to kill target cells. The structural and biochemical basis of antimicrobial lasso peptide MccJ25 binding to siderophore FhuA explains why these peptides have a narrow range of target species.
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Golgi sorting regulates organization and activity of GPI proteins at apical membranes pp350 - 357 Simona Paladino, Stéphanie Lebreton, Simona Tivodar, Fabio Formiggini, Giulia Ossato et al. doi:10.1038/nchembio.1495

High-resolution microscopy and biochemistry show that homoclusters of GPI-anchored proteins (GPI-APs) in the Golgi arrive at the apical membrane of polarized cells and then coalesce into larger heteroclusters. Therefore, sorting at the Golgi determines organization of GPI-APs at the plasma membrane.
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G-quadruplexes regulate Epstein-Barr virus–encoded nuclear antigen 1 mRNA translation pp358 - 364 Pierre Murat, Jie Zhong, Lea Lekieffre, Nathan P Cowieson, Jennifer L Clancy et al. doi:10.1038/nchembio.1479

Biophysical analysis reveals that conserved G-rich sequences within the mRNAs of gammaherpesvirus genome maintenance proteins (GMPs) form G-quadruplexes (G4). Stabilization of mRNA G4 motifs represses GMP translation, whereas destabilization enhances translation, suggesting that these RNA elements are cis-acting translational regulators of proteins involved in viral latency.
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Bacterial itaconate degradation promotes pathogenicity pp371 - 377 Jahminy Sasikaran, Michał Ziemski, Piotr K Zadora, Angela Fleig and Ivan A Berg doi:10.1038/nchembio.1482

Host cells respond to bacterial infection by producing itaconate, an inhibitor of bacterial metabolism, among other strategies. Biochemical characterization now defines genes known to be important for bacterial virulence as a new pathway that degrades itaconate into metabolic building blocks.
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Reversible [4Fe-3S] cluster morphing in an O2-tolerant [NiFe] hydrogenase pp378 - 385 Stefan Frielingsdorf, Johannes Fritsch, Andrea Schmidt, Mathias Hammer, Julia Löwenstein et al. doi:10.1038/nchembio.1500

Certain oxygen-tolerant hydrogenases contain a unique [4Fe-3S] cluster near the catalytic site, but the role of this cofactor is not fully understood. Crystallographic, spectroscopic and computational data now provide evidence for redox-dependent transformations of this cluster, potentially explaining how specialized hydrogenases can safely reduce inhibitory O2.
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Design of activated serine–containing catalytic triads with atomic-level accuracy pp386 - 391 Sridharan Rajagopalan, Chu Wang, Kai Yu, Alexandre P Kuzin, Florian Richter et al. doi:10.1038/nchembio.1498

De novo enzyme designs have generally tried to optimize multiple aspects of enzyme function simultaneously. Focusing only on positioning of active site residues to generate a nucleophilic serine as assessed by activity-based protein profiling now leads to a successful intermediate design.
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Bioretrosynthetic construction of a didanosine biosynthetic pathway pp392 - 399 William R Birmingham, Chrystal A Starbird, Timothy D Panosian, David P Nannemann, T M Iverson et al. doi:10.1038/nchembio.1494

Bioretrosynthesis is meant to simplify construction of metabolic pathways by screening only for the final desired product. This approach, aided by protein design and crystallography, is now used to synthesize an antiretroviral nucleoside analog and surprisingly identifies a new enzyme function. Chemical compounds
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Amphotericin forms an extramembranous and fungicidal sterol sponge pp400 - 406 Thomas M Anderson, Mary C Clay, Alexander G Cioffi, Katrina A Diaz, Grant S Hisao et al. doi:10.1038/nchembio.1496

NMR structural data and biophysical and biological experiments show that the antifungal compound amphotericin is toxic because it acts as a sterol sponge by interacting with ergosterol on the fungal membrane and extracting it from within the membrane to the surface of the membrane.
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