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Volume 16 Issue 2, February 2009

Fatty acid synthase is composed of several catalytic domains that work in sequence. Asturias and colleagues use single-particle EM analysis of rat FAS to reveal the movements of the domains during the reaction cycle. The cover image of a flamenco dancer represents the complex motions of FAS in action (© Emanuele Ferrari, iStockphoto). pp 190-197


  • Now that we are well into 2009, I can't help but think about the year that has passed. Fear not, this will not be one of those dreaded holiday letters where we list all the highs and lows of the year. But as I look back, there are many things I hope that I have permanently crossed off my 'To Do' list and others that I am looking forward to doing.



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News & Views

  • Large, multisubunit complexes have been implicated in tethering transport vesicles to organelle membranes before membrane fusion. New structures add to the growing list of tethering complexes that contain conserved helical bundle structures and provide a first glimpse of how these complexes are assembled.

    • Mary Munson
    News & Views
  • The DNA-repair machinery is faced with the significant challenge of differentiating DNA lesions from unmodified DNA. Two recent publications, one in this issue of Nature Structural & Molecular Biology, uncover a new way of recognizing minimally distorting DNA lesions: insertion of a 3- or 4-amino-acid wedge into DNA to extrude the lesion into a shallow binding pocket that can accommodate various damaged bases.

    • Orlando D Schärer
    • Arthur J Campbell
    News & Views
  • MukBEF, the bacterial prototype of eukaryotic condensins and cohesins, has a key role in the global chromosomal organization of Escherichia coli and its close relatives. The recent report of the crystal structure of the MukB head domain in complex with its accessory subunits MukEF clearly demonstrates that MukBEF functions as a macromolecular assembly rather than a set of individual molecules and offers clues on how ATP and MukEF regulate the architecture of this complex.

    • Valentin V Rybenkov
    News & Views
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  • The Dsl1p tethering complex is crucial for Golgi-to-ER retrograde trafficking of vesicles in yeast. The crystal structures of two out of three Dsl1p complex components reveal similarity to exocyst and COG complex components, which act in tethering vesicles to the plasma membrane and Golgi, respectively, suggesting a conserved tethering strategy at several eukaryotic membranes.

    • Arati Tripathi
    • Yi Ren
    • Frederick M Hughson
  • DNA packaging into nucleosomes presents a barrier to many motor proteins, including the transcriptional machinery. By unzipping DNA in single nucleosomes, a detailed map at near base pair resolution of histone-DNA interactions is now provided, suggesting that interaction with the two DNA strands is decoupled and that unraveling past the dyad axis of the nucleosome, as might occur when a motor protein passes through, is sufficient to displace histones.

    • Michael A Hall
    • Alla Shundrovsky
    • Michelle D Wang
  • Endonuclease V can initiate the repair of deaminated purine bases by recognizing them and hydrolyzing the second phosphodiester bond on their 3′ side. Now the crystal structures of endonuclease V in complex with its substrate and its product reveal a wedge motif acting as a minor groove–damage sensor and a pocket to recognize the lesion; the enzyme remains tightly bound to the 5′ phosphate product, perhaps to hand it over to downstream repair factors.

    • Bjørn Dalhus
    • Andrew S Arvai
    • Magnar Bjørås
  • Nucleosomes can be closely spaced in vivo, suggesting that they may on occasion approach one another or even meet. Using in vitro dinucleosomal model systems, positioned nucleosomes, as well as nucleosomes in the process of being repositioned, are now shown to overlap, forming single, compact particles, with one histone dimer ejected in the process. The potential relevance to remodeling processes is discussed.

    • Maik Engeholm
    • Martijn de Jager
    • Tom Owen-Hughes
  • Triple expansions underlie a number of human disorders. Triplet repeat instability in yeast mutants for the Srs2 and Sgs1 helicases indicate that recombination underlies instability in such a genetic background. Further analysis of replication intermediates indicates that Srs2 is likely to be involved in replication fork reversal within repetitive sequences, a process involved in preventing repeat instability and fragility.

    • Alix Kerrest
    • Ranjith P Anand
    • Guy-Franck Richard
  • Endonuclease V can initiate the repair of deaminated purine bases by recognizing them and hydrolyzing the second phosphodiester bond on their 3′ side. Now the crystal structures of endonuclease V in complex with its substrate and its product reveal a wedge motif acting as a minor groove–damage sensor and a pocket to recognize the lesion; the enzyme remains tightly bound to the 5′ phosphate product, perhaps to hand it over to downstream repair factors.

    • Shivani Ahuja
    • Viktor Hornak
    • Markus Eilers
  • One of the key early steps in splicing is recognition of the 5′ splice site by base-pairing to the U1 small nuclear RNA. Data now indicate that U1 can shift to recognize what had been designated as atypical 5′ splice sites, broadening the scope of what can be recognized as a functional splice site by the canonical machinery and thus impacting both splicing predictions and mechanism, as well as providing a potential mechanism underlying a puzzling mutation associated with pontocerebellar hypoplasia.

    • Xavier Roca
    • Adrian R Krainer
  • Small RNAs are involved in the regulation of gene expression. During a hunt for microRNAs in the simple chordate Ciona intestinalis, a distinct class of small RNAs, offset from the microRNA expressed from a given hairpin, have been defined. These offset small RNAs are expressed in relative abundance in C. intestinalis and are also detected at specific developmental stages. Although their function is unclear, these results suggest that microRNA processing has distinct properties in this simple organism.

    • Weiyang Shi
    • David Hendrix
    • Benjamin Haley
  • Fatty acid synthase is composed by several catalytic domains that work in sequence, with reaction intermediates being transferred between them. Single-particle EM analysis of different catalytic mutants of rat FAS imaged in the presence of substrates reveals the domains' movements during the reaction cycle.

    • Edward J Brignole
    • Stuart Smith
    • Francisco J Asturias
  • MIA40, found in the mitochondrial intermembrane space, is a central component in the import system that transports certain cysteine motif–containing proteins into the mitochondria. New analyses reveal that MIA40 forms a novel thioredoxin fold. Its redox center catalyzes the formation of the first disulfide bond of a substrate, causing the susbtrate's second disulfide to require only oxygen for its formation.

    • Lucia Banci
    • Ivano Bertini
    • Kostas Tokatlidis
  • RDE-1 is a Caenorhabditis elegans Argonaute homolog involved in mediating the primary response to small RNA interference. Analyses now indicate that the RNase H–homologous region of RDE-1 is not needed for target cleavage, but is specifically required for removing the passenger strand of fully complementary siRNA duplexes.

    • Florian A Steiner
    • Kristy L Okihara
    • René F Ketting
  • Nucleic acid polymerases catalyze nucleotidyl transfer reactions with two proton-transfer events, deprotonation of the 3′-hydroxyl nucleophile and protonation of the pyrophosphate leaving group. Functional analyses now show that the proton donor for the latter transfer is an active-site residue.

    • Christian Castro
    • Eric D Smidansky
    • Craig E Cameron
  • Activation of the 20S proteasome requires the binding of regulatory proteins such as the 19S regulatory particle, which opens the 20S gates allowing substrate access to the active sites. New data now indicate that binding of a polyubiquitylated substrate to the 19S particle allows further opening of the 20S gates, suggesting a feedforward mechanism for 20S activation.

    • Dawadschargal Bech-Otschir
    • Annett Helfrich
    • Peter-Michael Kloetzel
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Brief Communication

  • Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. These repeats adopt unusual structures that block DNA replication in vitro and in unicellular organisms. Mirkin and co-workers asked whether the same holds true in mammalian cells. They find that CGG repeats stall replication forks in a length-dependent, but orientation-independent, manner and do not seem to trigger an intra–S phase checkpoint response. They suggest that fragile sites arise because the cell cycle continues before replication is complete and the under-replicated areas would convert into constrictions and/or double-stranded breaks.

    • Irina Voineagu
    • Christine F Surka
    • Sergei M Mirkin
    Brief Communication
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