Nature Chemical Biology Contents: December 2013 Volume 9 Number 12 pp 747 - 848

TABLE OF CONTENTS December 2013 Volume 9, Issue 12 Focus Editorial Commentary Research Highlights News and Views Perspective Reviews Brief Communication Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Subscribe to Nature this Holiday season for only $50, £50 or €50 Enjoy 51 issues in print, online and multimedia content, and access via the nature.com app for iPhone, iPod touch and the new issue-based NatureJournals iPad app with enhanced features.  Subscribe today!    Focus Top Peptides in Immunology Peptides play a role in all aspects of the immunological responses to invading pathogens and tumor cells. The review, perspective and commentary pieces in this issue explore the generation and molecular mechanisms of peptides and the considerations and strategies needed to harness them to treat disease. Peptides in Immunology Editorial Top Mobilizing peptides in immunity   p747 doi:10.1038/nchembio.1409 Harnessing the immune system to treat disease will be facilitated by a greater understanding of the origins and roles of peptides in immunity. Commentary Top Designing immunogenic peptides   pp749 - 753 Darren R Flower doi:10.1038/nchembio.1383 Peptides fulfill many roles in immunology, yet none are more important than their role as immunogenic epitopes driving the adaptive immune response, our ultimate bulwark against infectious disease. Peptide epitopes are mediated primarily by their interaction with major histocompatibility complexes (T-cell epitopes) and antibodies (B-cell epitopes). As pathogen genomes continue to be revealed, both experimental and computational epitope mapping are becoming crucial tools in vaccine discovery. Immunoinformatics offers many tools, techniques and approaches for in silico epitope characterization, which is capable of greatly accelerating epitope design. Research Highlights Top Regeneration: Reversing MS | Glycobiology: Mimi mimicry | Epigenetics: RNA takes control | Prokaryotic immunology: A measure of RNA | Protein dynamics: Pomp and SERCAmstance | Metabolism: AMP is the champ | Reaction discovery: Now we're clicking | Metal regulation: SOD1 off zinc News and Views Top Enzyme mechanisms: What's up 'Doc'?   pp756 - 757 Wolfgang Peti and Rebecca Page doi:10.1038/nchembio.1379 The Doc-Phd pair forms a bacterial toxin-antitoxin system, but the mechanism by which the Fic-family member Doc causes toxicity is not fully defined. New research shows that Doc unexpectedly functions as a kinase to phosphorylate elongation factor TU, thus inhibiting translation and leading to Doc-mediated growth arrest. See also: Article by Castro-Roa et al. Immunology: Allergy's Achilles' heel?   pp757 - 759 Brian J Sutton doi:10.1038/nchembio.1390 Allergic reactions to otherwise innocuous substances involve a complex interplay of molecular interactions[mdash]some strong, some weak. This study reveals a key role for low-affinity antibodies and thus a possible point of weakness that may be exploited for therapeutic intervention. See also: Article by Handlogten et al. Antigenic peptides: Reviving nuclear translation   pp759 - 760 Petra Van Damme and Gerben Menschaert doi:10.1038/nchembio.1394 Noncanonical translation of prespliced mRNA provides physiological meaning to nuclear translation in generating antigenic peptide substrates for the endogenous major histocompatibility complex class I pathway. Chemical Biology JOBS of the week Senior Faculty Position in Chemical Biology University of Utah Postdoctoral Position - Chemical Biology and Proteomics Laboratory, Salk Institute The Salk Institute for Biological Studies More Science jobs from Chemical Biology EVENT Chemical Biology Discussion Group Year-End Symposium 3 June 2014 New York, USA More science events from Perspective Top Immune modulation by multifaceted cationic host defense (antimicrobial) peptides   pp761 - 768 Ashley L Hilchie, Kelli Wuerth and Robert E W Hancock doi:10.1038/nchembio.1393 Reviews Top A peptide's perspective on antigen presentation to the immune system   pp769 - 775 Jacques Neefjes and Huib Ovaa doi:10.1038/nchembio.1391 Adaptive immune activation: glycosylation does matter   pp776 - 784 Margreet A Wolfert and Geert-Jan Boons doi:10.1038/nchembio.1403 Brief Communication Top Development of small-molecule inhibitors targeting adipose triglyceride lipase   pp785 - 787 Nicole Mayer, Martina Schweiger, Matthias Romauch, Gernot F Grabner, Thomas O Eichmann et al. doi:10.1038/nchembio.1359 A competitive inhibitor of the lipase ATGL reduces the availability of adipocyte fatty acids, causing insulin resistance in insulin-sensitive tissues. Chemical compounds Articles Top Inhibition of weak-affinity epitope-IgE interactions prevents mast cell degranulation   pp789 - 795 Michael W Handlogten, Tanyel Kiziltepe, Ana P Serezani, Mark H Kaplan and Basar Bilgicer doi:10.1038/nchembio.1358 A set of tetravalent antigens reveals that low-affinity interactions between an allergen epitope and IgE antibodies contribute to allergic responses through FcɛRI receptors on mast cells, and inhibiting these low-affinity epitopes prevents degranulation. Chemical compounds See also: News and Views by Sutton Metabolic suppression identifies new antibacterial inhibitors under nutrient limitation   pp796 - 804 Soumaya Zlitni, Lauren F Ferruccio and Eric D Brown doi:10.1038/nchembio.1361 Identification of antibacterials and then their mechanism of action using metabolic suppression profiling uncovers inhibitors targeting glycine metabolism, PABA and biotin biosynthesis. Chemical compounds An in vitro evolved glmS ribozyme has the wild-type fold but loses coenzyme dependence   pp805 - 810 Matthew W L Lau and Adrian R Ferré-D'Amaré doi:10.1038/nchembio.1360 The bacterial glmS riboswitch is unique in that the bound glucosamine-6-phosphate ligand acts as a cofactor for ribozyme-mediated RNA cleavage. In vitro selection and crystallographic analysis reveal that three mutations convert glmS from a cofactor-dependent to a metal ion–dependent ribozyme. The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-Tu   pp811 - 817 Daniel Castro-Roa, Abel Garcia-Pino, Steven De Gieter, Nico A J van Nuland, Remy Loris et al. doi:10.1038/nchembio.1364 The Doc-Phd toxin-antitoxin system inhibits bacterial translation via an unknown mechanism. Functional and structural analyses now show that Doc, which has an active site like AMPylating Fic proteins, actually works as a kinase, phosphorylating EF-Tu to block translation. See also: News and Views by Peti & Page Distinct mechanisms for spiro-carbon formation reveal biosynthetic pathway crosstalk   pp818 - 825 Yuta Tsunematsu, Noriyasu Ishikawa, Daigo Wakana, Yukihiro Goda, Hiroshi Noguchi et al. doi:10.1038/nchembio.1366 Spiran rings appear in numerous natural products, but the mechanism of their formation is not always clear. Reconstitution of the spirotryprostatin pathway now reveals that distinct biochemical mechanisms, one catalyzed by an enzyme from an unrelated pathway, lead to related spiran-containing structures. Chemical compounds Elementary tetrahelical protein design for diverse oxidoreductase functions   pp826 - 833 Tammer A Farid, Goutham Kodali, Lee A Solomon, Bruce R Lichtenstein, Molly M Sheehan et al. doi:10.1038/nchembio.1362 Assembled helical maquettes have been used to mimic basic oxidoreductase activities, but the requisite design symmetry limited advanced functions. Construction of a single-chain protein now enables intra- and interprotein electron transfer and complex cofactor interactions at rates comparable to those of natural proteins. Riboswitches in eubacteria sense the second messenger c-di-AMP   pp834 - 839 James W Nelson, Narasimhan Sudarsan, Kazuhiro Furukawa, Zasha Weinberg, Joy X Wang et al. doi:10.1038/nchembio.1363 Cyclic diadenosine monophosphate (c-di-AMP) is a newly identified nucleotide second messenger in bacteria. Though protein receptors for c-di-AMP are known, the ydaO riboswitch has now been validated as a physiological sensor of cellular c-di-AMP levels. Niche-based screening identifies small-molecule inhibitors of leukemia stem cells   pp840 - 848 Kimberly A Hartwell, Peter G Miller, Siddhartha Mukherjee, Alissa R Kahn, Alison L Stewart et al. doi:10.1038/nchembio.1367 High-throughput screening systems that better mimic the physiological complexity of diseased tissues may aid the discovery of more efficacious compounds. A co-culture system that mimics the microenvironment of leukemia stem cells (LSCs) in bone marrow enables the discovery of compounds, including lovastatin, that selectively kill LSCs. Chemical compounds Top Advertisement The Journal of Antibiotics presents you a Chemistry and Biology of secondary metabolites, natural product genomics, actinomycete bioactive metabolites -a tribute to Professor Leo Vining, in which Leo Vinings friends and past colleagues pay tribute to his legacy in a series of articles inspired by his vision and his example.  Access select articles FREE for a limited-time!    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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