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FEBS Journal

Cover image for Vol. 280 Issue 22

November 2013

Volume 280, Issue 22

Pages i–iii, 5569–5935

  1. Front Cover

    1. Top of page
    2. Front Cover
    3. Editorial Information
    4. Minireview Series
    5. Minireviews
    6. Review Article
    7. Regular Papers
    8. Author index
    9. Table of Contents
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      Front Cover (page i)

      Article first published online: 24 OCT 2013 | DOI: 10.1111/j.1742-4658.2013.08802.x

      Thumbnail image of graphical abstract

      Microfluidics-Enabled TRESI-HDX Reveals the Dynamic Basis of Protein Function and Interaction Networks. This figure was provided by Derek York (University Toronto, Canada) especially for the issue.

  2. Editorial Information

    1. Top of page
    2. Front Cover
    3. Editorial Information
    4. Minireview Series
    5. Minireviews
    6. Review Article
    7. Regular Papers
    8. Author index
    9. Table of Contents
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      Editorial Information (pages ii–iii)

      Article first published online: 24 OCT 2013 | DOI: 10.1111/j.1742-4658.2013.08802_1.x

  3. Minireview Series

    1. Top of page
    2. Front Cover
    3. Editorial Information
    4. Minireview Series
    5. Minireviews
    6. Review Article
    7. Regular Papers
    8. Author index
    9. Table of Contents
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      Dynamic proteins: changes in structures, activities and networks (page 5569)

      Lisa M. Miller Jenkins and Daniel Figeys

      Article first published online: 22 OCT 2013 | DOI: 10.1111/febs.12548

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      The minireview series represents a sampling of work presented at the 2012 Methods in Protein Structure Analysis meeting held in Ottawa, Canada. Within the 11 minireviews are methods for studying proteins in vitro and within the context of the cell. This series offers a window into the dynamics of protein conformation, regulation, and function.

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  4. Minireviews

    1. Top of page
    2. Front Cover
    3. Editorial Information
    4. Minireview Series
    5. Minireviews
    6. Review Article
    7. Regular Papers
    8. Author index
    9. Table of Contents
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      Structure and mechanism of non-histone protein acetyltransferase enzymes (pages 5570–5581)

      David R. Friedmann and Ronen Marmorstein

      Article first published online: 28 JUN 2013 | DOI: 10.1111/febs.12373

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      The structure of protein acetyltransferases (PATs) has provided molecular information on their structural features, enzymatic mechanisms, substrate-specific recognition and regulatory elements. Here, we describe non-histone protein substrates and the structure of PATs to compare and contrast them with histone acetyltransferases to better understand the molecular basis for protein recognition and modification by this burgeoning family of protein modification enzymes.

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      Modulating protein stability – directed evolution strategies for improved protein function (pages 5582–5595)

      Raymond D. Socha and Nobuhiko Tokuriki

      Article first published online: 18 JUN 2013 | DOI: 10.1111/febs.12354

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      Often, the functional adaptation or optimization of a protein through directed evolution produces a less than desirable result. By utilizing techniques that modulate the stability of a protein during the course of its function-related directed evolution, an improved result may be attained. Herein, we describe two general approaches to achieve this and detail an effective combinatorial approach.

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      Structural and functional importance of local and global conformational fluctuations in the RNase A superfamily (pages 5596–5607)

      Donald Gagné and Nicolas Doucet

      Article first published online: 24 JUN 2013 | DOI: 10.1111/febs.12371

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      It has been postulated that protein homologues have evolved similar dynamic fluctuations to promote catalytic function, a property that would presumably be encoded in their structural fold. In this review, we explore this hypothesis by comparing the numerous and diverse flexibility reports available for a number of structural and functional homologues of the pancreatic-like RNase A superfamily.

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      Role of conformational entropy in the activity and regulation of the catalytic subunit of protein kinase A (pages 5608–5615)

      Gianluigi Veglia and Alessandro Cembran

      Article first published online: 27 AUG 2013 | DOI: 10.1111/febs.12462

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      Here, we review our latest NMR studies on the C subunit of the protein kinase A, underscoring the role of fast and slow conformational dynamics in both the activation and inhibition of the kinase.

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      Characterizing rapid, activity-linked conformational transitions in proteins via sub-second hydrogen deuterium exchange mass spectrometry (pages 5616–5625)

      Diana Resetca and Derek J. Wilson

      Article first published online: 11 JUN 2013 | DOI: 10.1111/febs.12332

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      This review outlines the application of time-resolved electrospray ionization mass spectrometry (TRESI-MS) and hydrogen-deuterium exchange (HDX) to study rapid, activity-linked conformational transitions in proteins. Implementation on a microfluidic chip incorporates all sample handling steps required for a ‘bottom-up’ HDX workflow. Combining short HDX labeling pulses with rapid digestion enables the detailed characterization of structural transitions in diverse biochemical processes.

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      Proteomics methods for subcellular proteome analysis (pages 5626–5634)

      Romain Drissi, Marie-Line Dubois and François-Michel Boisvert

      Article first published online: 20 SEP 2013 | DOI: 10.1111/febs.12502

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      The elucidation of the subcellular distribution of proteins under different conditions is a major challenge in cell biology. This challenge is further complicated by the multicompartmental and dynamic nature of protein localization. Here, we review quantitative mass spectrometry-based approaches which combine cellular fractionation with proteomic analysis.

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      The application of proteomic approaches to the study of mammalian spermatogenesis and sperm function (pages 5635–5651)

      Graham MacLeod and Susannah Varmuza

      Article first published online: 2 SEP 2013 | DOI: 10.1111/febs.12461

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      Spermatogenesis is a complex developmental process involving numerous germ cell types, that to date cannot be fully modelled in culture. Proteomic approaches have played an instrumental role in our understanding of spermatogenesis and sperm function. This article reviews existing proteomic literature and available datasets regarding the proteomic characterization of spermatogenic cell types, subcellular proteomics, post-translational modifications, interactomes and clinical studies.

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      Targeted lipidomics – advances in profiling lysophosphocholine and platelet-activating factor second messengers (pages 5652–5667)

      Hongbin Xu, Nicolas Valenzuela, Stephen Fai, Daniel Figeys and Steffany A. L. Bennett

      Article first published online: 29 JUL 2013 | DOI: 10.1111/febs.12423

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      Glycerophospholipids are the major building blocks of biological membranes and the precursors of lipid second messengers. Alterations in the lipid signalling are implicated in a number of human diseases. Targeted lipidomics is enabling the molecular identification and quantification of these low-abundance second messengers and providing valuable insight into the roles of the cellular lipidome in cell function and disease susceptibility.

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      Recent technological developments in proteomics shed new light on translational research on diabetic microangiopathy (pages 5668–5681)

      Yuhang Ma, Cheng Yang, Yimin Tao, Hu Zhou and Yufan Wang

      Article first published online: 27 JUN 2013 | DOI: 10.1111/febs.12369

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      Diabetic microangiopathy has become a heavy social burden. At present, it is still difficult to predict and diagnose this ailment at an early stage. Proteomic analyses have been used for find the biomarkers in diabetic microangiopathy. In this review, we briefly introduce the recent technological developments in proteomics methods and summarize current proteomic-based, translational research on diabetic microangiopathy.

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      Network biomarkers reveal dysfunctional gene regulations during disease progression (pages 5682–5695)

      Tao Zeng, Shao-yan Sun, Yong Wang, Hailong Zhu and Luonan Chen

      Article first published online: 22 OCT 2013 | DOI: 10.1111/febs.12536

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      Here, we briefly report on the state-of-the-art research and application of biomarkers from single genes to gene sets, gene networks and dynamical gene networks, which explore the increasingly-accumulated gene expression and sequence data. Differential network biomarkers and dynamical network biomarkers are used as representative examples to demonstrate their effectiveness on detecting early signals for complex diseases and revealing essential pathogen mechanisms.

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      Phosphoproteomics-based network medicine (pages 5696–5704)

      Zexian Liu, Yongbo Wang and Yu Xue

      Article first published online: 28 JUN 2013 | DOI: 10.1111/febs.12380

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      We summarized the current efforts and progress in phosphoproteomics-based network medicine by reviewing the computational (re)construction of phosphorylation-mediated signaling networks from unannotated phosphoproteomic data, the discovery of robust network phospho-signatures, and the application of these signatures for classifying cancers and predicting drug responses. We anticipated that such a systematic approach can generate more useful biomarkers for biomedical usage.

  5. Review Article

    1. Top of page
    2. Front Cover
    3. Editorial Information
    4. Minireview Series
    5. Minireviews
    6. Review Article
    7. Regular Papers
    8. Author index
    9. Table of Contents
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      Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination (pages 5705–5736)

      Alexander Wlodawer, Wladek Minor, Zbigniew Dauter and Mariusz Jaskolski

      Article first published online: 18 SEP 2013 | DOI: 10.1111/febs.12495

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      This review, addressed to the less experienced macromolecular crystallographers and to users of biological structures, provides an outline of the technical aspects of crystallography, and discusses common problems and pitfalls encountered during structure determination and interpretation. It includes tips on how to interpret, but not overinterpret, the information present in the coordinate files and in their description.

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  6. Regular Papers

    1. Top of page
    2. Front Cover
    3. Editorial Information
    4. Minireview Series
    5. Minireviews
    6. Review Article
    7. Regular Papers
    8. Author index
    9. Table of Contents
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      The 2-oxoglutarate supply exerts significant control on the lysine synthesis flux in Saccharomyces cerevisiae (pages 5737–5749)

      Héctor Quezada, Alvaro Marín-Hernández, Roberto Arreguín-Espinosa, Franklin D. Rumjanek, Rafael Moreno-Sánchez and Emma Saavedra

      Article first published online: 13 SEP 2013 | DOI: 10.1111/febs.12490

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      The elasticity analysis approach of metabolic control analysis was applied to determine what controls the flux of lysine synthesis in Saccharomyces cerevisiae. The flux control coefficients for the 2-oxoglutarate supplier group of reactions, and the lysine and glutamate syntheses pathways, were 1.1, 0.41 and −0.52, respectively. This indicated that lysine synthesis was mainly controlled by the supply of the precursor 2-oxoglutarate.

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      Comparison of complexes formed by a crustacean and a vertebrate trypsin with bovine pancreatic trypsin inhibitor – the key to achieving extreme stability? (pages 5750–5763)

      Tamás Molnár, Judit Vörös, Bálint Szeder, Kornél Takáts, József Kardos, Gergely Katona and László Gráf

      Article first published online: 13 SEP 2013 | DOI: 10.1111/febs.12491

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      The complex formed between crayfish trypsin and bovine pancreatic trypsin inhibitor shows unusually high resistance against heating and chemical denaturing agents. In this study, we present biophysical and structural comparisons of structurally highly homologous trypsins and trypsin–trypsin inhibitor complexes to explore what special features are responsible for this extreme stability. Results could be profitable for further protein engineering studies.

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      Unraveling enzyme discrimination during cellulosome assembly independent of cohesindockerin affinity (pages 5764–5779)

      Romain Borne, Edward A. Bayer, Sandrine Pagès, Stéphanie Perret and Henri-Pierre Fierobe

      Article first published online: 10 SEP 2013 | DOI: 10.1111/febs.12497

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      Random assembly of bacterial cellulosomes was examined by mixing enzymes with same dockerins with a scaffoldin hosting identical cohesins. Only three types of complexes were formed out of ten possible combinations. Furthermore, the preferential integration of enzymes appears to be related to the length of the inter-cohesin linkers. Thus, bacterial cellulosomes are not necessarily assembled at random.

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      The transporter–opsin–G protein-coupled receptor (TOG) superfamily (pages 5780–5800)

      Daniel C. Yee, Maksim A. Shlykov, Åke Västermark, Vamsee S. Reddy, Sumit Arora, Eric I. Sun and Milton H. Saier Jr

      Article first published online: 23 SEP 2013 | DOI: 10.1111/febs.12499

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      The TOG superfamily is believed to have arisen from a 4-TMS precursor that duplicated to an 8-TMS precursor, common to the superfamily constituents, before diverging in topology via the loss or gain of specific TMSs. The 4-TMS duplication may have occurred more than once during the TOG superfamily evolution. This pathway does not exclude other possible routes.

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      PPARγ forms a bridge between DNA methylation and histone acetylation at the C/EBPα gene promoter to regulate the balance between osteogenesis and adipogenesis of bone marrow stromal cells (pages 5801–5814)

      Qing-hua Zhao, Shou-guo Wang, Shao-xian Liu, Ji-peng Li, Yong-xing Zhang, Zhong-yi Sun, Qi-ming Fan and Ji-wei Tian

      Article first published online: 13 SEP 2013 | DOI: 10.1111/febs.12500

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      The balance between osteogenesis and adipogenesis of BMSC is impaired in many diseases. The current study provides insights into the mechanisms underlying the balance between osteogenesis and adipogenesis regulated by PPARγ in synergy with C/EBPα and illustrates a molecular model about how DNA methylation and histone acetylation at C/EBPα promoter are linked by PPARγ to regulate BMSC differentiation.

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      Biochemical and structural characterization of a novel bacterial manganese-dependent hydroxynitrile lyase (pages 5815–5828)

      Ivan Hajnal, Andrzej Łyskowski, Ulf Hanefeld, Karl Gruber, Helmut Schwab and Kerstin Steiner

      Article first published online: 18 SEP 2013 | DOI: 10.1111/febs.12501

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      Hydroxynitrile lyases are used in biocatalysis to catalyse the synthesis of enantiopure cyanohydrins, which are versatile building blocks in chemical industry. We report on the detailed biochemical and structural characterisation of a metal-dependent HNL from Granulicella tundricola, which was successfully heterologously expressed in E. coli. The crystal structure was solved at a crystallographic resolution of 2.5 Å and exhibits a cupin fold.

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      Structure–activity relationship analysis of curcumin analogues on anti-influenza virus activity (pages 5829–5840)

      Jun-Lin Ou, Yoshiyuki Mizushina, Sheng-Yang Wang, Duen-Yau Chuang, Muthukumar Nadar and Wei-Li Hsu

      Article first published online: 23 SEP 2013 | DOI: 10.1111/febs.12503

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      We demonstrated two curcumin derivatives (Pet and THC) exhibit anti-influenza virus activity. Structure-activity relationship analysis revealed that the two-enone functional groups, as an acceptor of Michael addition conjugation, attribute to the differential inhibitory effect of curcuminoids. Collectively, experimental evidences and in silico docking simulation indicated that curcumin effectively blocks influenza entry by interrupting the interaction of HA protein with cellular receptor.

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      Towards the rational design of antimicrobial proteins: Single point mutations can switch on bactericidal and agglutinating activities on the RNase A superfamily lineage (pages 5841–5852)

      David Pulido, Mohammed Moussaoui, M. Victòria Nogués, Marc Torrent and Ester Boix

      Article first published online: 8 OCT 2013 | DOI: 10.1111/febs.12506

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      We have designed an EDN double mutant, Q34R/R35W, which displays enhanced bactericidal activity and a significant increase on lipopolysaccharide affinity. One additional mutation, T13I, provides EDN with an exposed hydrophobic patch required for self-aggregation that triggers bacteria agglutination. Our results highlight how structure guided protein engineering can successfully reproduce an evolution selection process towards the emergence of new physiological roles.

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      ATP binding to human serine racemase is cooperative and modulated by glycine (pages 5853–5863)

      Marialaura Marchetti, Stefano Bruno, Barbara Campanini, Alessio Peracchi, Nicole Mai and Andrea Mozzarelli

      Article first published online: 25 SEP 2013 | DOI: 10.1111/febs.12510

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      NMDA receptors are modulated by the co-agonists glycine and D-serine, the latter being synthesized by serine racemase. Binding of the allosteric ligand ATP to the enzyme is strongly cooperative. Glycine, a substrate analog, increases ATP affinity and abolishes cooperativity. These results support the notion of a crosstalk between allosteric and active sites and the existence of alternative protein conformations.

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      Excess fructose intake-induced hypertrophic visceral adipose tissue results from unbalanced precursor cell adipogenic signals (pages 5864–5874)

      María G. Zubiría, Juan P. Fariña, Griselda Moreno, Juan J. Gagliardino, Eduardo Spinedi and Andrés Giovambattista

      Article first published online: 23 SEP 2013 | DOI: 10.1111/febs.12511

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      Three week-fed male rats with commercial diet plus 10% fructose in the drinking water (FRD) displayed an increased activity of their visceral adipose tissue (VAT) precursor cells and VAT mass/cell size. Since FRD did not modify VAT precursor cell population, the increased adipogenesis would result from an imbalance between endogenous pro- and anti-adipogenic SVF cell signals, shifted towards the former.

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      The excluded volume effect induced by poly(ethylene glycol) modulates the motility of actin filaments interacting with myosin (pages 5875–5883)

      Shinsuke Munakata and Kuniyuki Hatori

      Article first published online: 23 SEP 2013 | DOI: 10.1111/febs.12513

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      Increased concentrations and molecular weights of PEG decreased the sliding velocity of both actin and regulated thin filaments on myosin molecules. The decreased ratio of velocity in regulated thin filaments at pCa 4 was higher than that of actin filaments. The conformation of the surface of filaments decorated with Tn-Tm affects the excluded volume for actomyosin interactions.

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      Resistin affects lipid metabolism during adipocyte maturation of 3T3-L1 cells (pages 5884–5895)

      Yoshito Ikeda, Hiroyuki Tsuchiya, Susumu Hama, Kazuaki Kajimoto and Kentaro Kogure

      Article first published online: 25 SEP 2013 | DOI: 10.1111/febs.12514

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      In the present study, we found that lipid content was significantly decreased in 3T3-L1 cells transfected with anti-resistin siRNA after adipocyte differentiation. In addition, protein expression and transcriptional activity levels of carbohydrate response element-binding protein (ChREBP), which upregulates transcription of lipogenic genes, decreased after anti-resistin siRNA treatment. These results suggest that resistin may affect lipid metabolism during adipocyte maturation.

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      Mechanistic insights into 1-deoxy-d-xylulose 5-phosphate reductoisomerase, a key enzyme of the MEP terpenoid biosynthetic pathway (pages 5896–5905)

      Heng Li, Jie Tian, Wei Sun, Wei Qin and Wen-Yun Gao

      Article first published online: 24 OCT 2013 | DOI: 10.1111/febs.12516

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      A C3–C4 DXP binding mode and a catalytic cycle for DXR are established. Taking into account the binding mode of DXP and the catalytic cycle of DXR, the mechanistic insights of DXR are disclosed and the current discrepancies concerning the catalysis of this enzyme are interpreted within the accepted retro-aldol/aldol sequence.

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      Amino acid residues crucial for specificity of toxin–antitoxin interactions in the homologous Axe–Txe and YefM–YoeB complexes (pages 5906–5918)

      Dorota Połom, Lidia Boss, Grzegorz Węgrzyn, Finbarr Hayes and Barbara Kędzierska

      Article first published online: 25 SEP 2013 | DOI: 10.1111/febs.12517

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      The specificity of interactions between toxins and antitoxins from homologous but non-interacting systems was investigated. Based on molecular modeling, selected amino acid residues were changed to assess which positions were crucial in specificity of toxin-antitoxin interactions in the related Axe-Txe and YefM-YoeB complexes. We conclude that Asp83 in Txe is crucial for specificity of toxin–antitoxin interactions in the Axe-Txe complex.

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      Role of Ca2+ in folding the tandem β-sandwich extender domains of a bacterial ice-binding adhesin (pages 5919–5932)

      Shuaiqi Guo, Christopher P. Garnham, Sarathy Karunan Partha, Robert L. Campbell, John S. Allingham and Peter L. Davies

      Article first published online: 11 OCT 2013 | DOI: 10.1111/febs.12518

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      The104-residue domain that occurs ~120 times as a direct tandem repeat in a 1.5 MDa ice-binding adhesin (MpAFP) has a Ca2+-dependent Ig-like fold. Based on the crystal structure we suggest Ca2+ also bridges these extender domains together to help project the ice-binding domain away from the surface of the host Antarctic bacterium towards ice.

  7. Author index

    1. Top of page
    2. Front Cover
    3. Editorial Information
    4. Minireview Series
    5. Minireviews
    6. Review Article
    7. Regular Papers
    8. Author index
    9. Table of Contents
    1. You have free access to this content
      Author index (page 5933)

      Article first published online: 24 OCT 2013 | DOI: 10.1111/j.1742-4658.2013.08801.x

  8. Table of Contents

    1. Top of page
    2. Front Cover
    3. Editorial Information
    4. Minireview Series
    5. Minireviews
    6. Review Article
    7. Regular Papers
    8. Author index
    9. Table of Contents
    1. You have free access to this content
      Table of Contents (pages 5934–5935)

      Article first published online: 24 OCT 2013 | DOI: 10.1111/febs.12573

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