Table of contents
February 2009, Volume 16 No 2 pp99-228
About the coverEditorial
The year that was and the year ahead - p99
doi:10.1038/nsmb0209-99
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.
Full Text - The year that was and the year ahead | PDF (256 KB) - The year that was and the year ahead
News and Views
Tip20p reaches out to Dsl1p to tether membranes - pp100 - 102
Mary Munson
doi:10.1038/nsmb0209-100
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.
Full Text - Tip20p reaches out to Dsl1p to tether membranes | PDF (1,631 KB) - Tip20p reaches out to Dsl1p to tether membranes
See also: Article by Tripathi et al.
Wedging out DNA damage - pp102 - 104
Orlando D Schärer & Arthur J Campbell
doi:10.1038/nsmb0209-102
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.
Full Text - Wedging out DNA damage | PDF (534 KB) - Wedging out DNA damage
See also: Article by Dalhus et al.
Towards the architecture of the chromosomal architects - pp104 - 105
Valentin V Rybenkov
doi:10.1038/nsmb0209-104
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.
Full Text - Towards the architecture of the chromosomal architects | PDF (162 KB) - Towards the architecture of the chromosomal architects
Research highlights - p106
doi:10.1038/nsmb0209-106
Full Text - Research highlights | PDF (145 KB) - Research highlights
Perspective
Nonsense-mediated mRNA decay (NMD) mechanisms - pp107 - 113
Saverio Brogna & Jikai Wen
doi:10.1038/nsmb.1550
Abstract - | Full Text - Nonsense-mediated mRNA decay (NMD) mechanisms | PDF (580 KB) - Nonsense-mediated mRNA decay (NMD) mechanisms
Articles
Structural characterization of Tip20p and Dsl1p, subunits of the Dsl1p vesicle tethering complex - pp114 - 123
Arati Tripathi, Yi Ren, Philip D Jeffrey & Frederick M Hughson
doi:10.1038/nsmb.1548
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.
Abstract - | Full Text - Structural characterization of Tip20p and Dsl1p, subunits of the Dsl1p vesicle tethering complex | PDF (1,129 KB) - Structural characterization of Tip20p and Dsl1p, subunits of the Dsl1p vesicle tethering complex | Supplementary information
See also: News and Views by Munson
High-resolution dynamic mapping of histone-DNA interactions in a nucleosome - pp124 - 129
Michael A Hall, Alla Shundrovsky, Lu Bai, Robert M Fulbright, John T Lis & Michelle D Wang
doi:10.1038/nsmb.1526
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.
Abstract - | Full Text - High-resolution dynamic mapping of histone-DNA interactions in a nucleosome | PDF (943 KB) - High-resolution dynamic mapping of histone-DNA interactions in a nucleosome | Supplementary information
An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells - pp130 - 137
Gene W Yeo, Nicole G Coufal, Tiffany Y Liang, Grace E Peng, Xiang-Dong Fu & Fred H Gage
doi:10.1038/nsmb.1545
Using CLIP-seq technology, the genome-wide binding sites of the FOX2 splicing regulator in human embryonic stem cells (hESCs) are now identified. Further work based on FOX2 depletion uncovers the underlying logic of FOX2-mediated regulation of alternative splicing and finds that such compromised hESCs undergo rapid cell death.
Abstract - | Full Text - An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells | PDF (2,752 KB) - An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells | Supplementary information
Structures of endonuclease V with DNA reveal initiation of deaminated adenine repair - pp138 - 143
Bjørn Dalhus, Andrew S Arvai, Ida Rosnes, Øyvind E Olsen, Paul H Backe, Ingrun Alseth, Honghai Gao, Weiguo Cao, John A Tainer & Magnar Bjørås
doi:10.1038/nsmb.1538
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.
Abstract - | Full Text - Structures of endonuclease V with DNA reveal initiation of deaminated adenine repair | PDF (826 KB) - Structures of endonuclease V with DNA reveal initiation of deaminated adenine repair | Supplementary information
See also: News and Views by Schärer & Campbell
Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs - pp144 - 150
Shuo Gu, Lan Jin, Feijie Zhang, Peter Sarnow & Mark A Kay
doi:10.1038/nsmb.1552
MicroRNA target sites tend to reside in the 3' untranslated regions of transcripts in animals. By altering the stop codon position in a model target and thus placing miRNA target sites within open reading frames, it is now found that translation through a miRNA target region is refractory to miRNA-mediated repression.
Abstract - | Full Text - Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs | PDF (565 KB) - Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs | Supplementary information
Nucleosomes can invade DNA territories occupied by their neighbors - pp151 - 158
Maik Engeholm, Martijn de Jager, Andrew Flaus, Ruth Brenk, John van Noort & Tom Owen-Hughes
doi:10.1038/nsmb.1551
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.
Abstract - | Full Text - Nucleosomes can invade DNA territories occupied by their neighbors | PDF (832 KB) - Nucleosomes can invade DNA territories occupied by their neighbors | Supplementary information
SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination - pp159 - 167
Alix Kerrest, Ranjith P Anand, Rangapriya Sundararajan, Rodrigo Bermejo, Giordano Liberi, Bernard Dujon, Catherine H Freudenreich & Guy-Franck Richard
doi:10.1038/nsmb.1544
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.
Abstract - | Full Text - SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination | PDF (802 KB) - SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination | Supplementary information
Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation - pp168 - 175
Shivani Ahuja, Viktor Hornak, Elsa C Y Yan, Natalie Syrett, Joseph A Goncalves, Amiram Hirshfeld, Martine Ziliox, Thomas P Sakmar, Mordechai Sheves, Philip J Reeves, Steven O Smith & Markus Eilers
doi:10.1038/nsmb.1549
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.
Abstract - | Full Text - Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation | PDF (890 KB) - Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation | Supplementary information
Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA - pp176 - 182
Xavier Roca & Adrian R Krainer
doi:10.1038/nsmb.1546
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.
Abstract - | Full Text - Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA | PDF (697 KB) - Recognition of atypical 5' splice sites by shifted base-pairing to U1 snRNA | Supplementary information
A distinct class of small RNAs arises from pre-miRNA–proximal regions in a simple chordate - pp183 - 189
Weiyang Shi, David Hendrix, Mike Levine & Benjamin Haley
doi:10.1038/nsmb.1536
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.
Abstract - | Full Text - A distinct class of small RNAs arises from pre-miRNA–proximal regions in a simple chordate | PDF (2,628 KB) - A distinct class of small RNAs arises from pre-miRNA–proximal regions in a simple chordate | Supplementary information
Conformational flexibility of metazoan fatty acid synthase enables catalysis - pp190 - 197
Edward J Brignole, Stuart Smith & Francisco J Asturias
doi:10.1038/nsmb.1532
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.
Abstract - | Full Text - Conformational flexibility of metazoan fatty acid synthase enables catalysis | PDF (1,038 KB) - Conformational flexibility of metazoan fatty acid synthase enables catalysis | Supplementary information
MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria - pp198 - 206
Lucia Banci, Ivano Bertini, Chiara Cefaro, Simone Ciofi-Baffoni, Angelo Gallo, Manuele Martinelli, Dionisia P Sideris, Nitsa Katrakili & Kostas Tokatlidis
doi:10.1038/nsmb.1553
PDB code
3D view
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.
Abstract - | Full Text - MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria | PDF (999 KB) - MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria | Supplementary information
RDE-1 slicer activity is required only for passenger-strand cleavage during RNAi in Caenorhabditis elegans - pp207 - 211
Florian A Steiner, Kristy L Okihara, Suzanne W Hoogstrate, Titia Sijen & René F Ketting
doi:10.1038/nsmb.1541
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.
Abstract - | Full Text - RDE-1 slicer activity is required only for passenger-strand cleavage during RNAi in Caenorhabditis elegans | PDF (419 KB) - RDE-1 slicer activity is required only for passenger-strand cleavage during RNAi in Caenorhabditis elegans | Supplementary information
Nucleic acid polymerases use a general acid for nucleotidyl transfer - pp212 - 218
Christian Castro, Eric D Smidansky, Jamie J Arnold, Kenneth R Maksimchuk, Ibrahim Moustafa, Akira Uchida, Matthias Götte, William Konigsberg & Craig E Cameron
doi:10.1038/nsmb.1540
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.
Abstract - | Full Text - Nucleic acid polymerases use a general acid for nucleotidyl transfer | PDF (639 KB) - Nucleic acid polymerases use a general acid for nucleotidyl transfer | Supplementary information
Polyubiquitin substrates allosterically activate their own degradation by the 26S proteasome - pp219 - 225
Dawadschargal Bech-Otschir, Annett Helfrich, Cordula Enenkel, Gesa Consiglieri, Michael Seeger, Hermann-Georg Holzhütter, Burkhardt Dahlmann & Peter-Michael Kloetzel
doi:10.1038/nsmb.1547
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.
Abstract - | Full Text - Polyubiquitin substrates allosterically activate their own degradation by the 26S proteasome | PDF (525 KB) - Polyubiquitin substrates allosterically activate their own degradation by the 26S proteasome | Supplementary information
Brief Communication
Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility - pp226 - 228
Irina Voineagu, Christine F Surka, Alexander A Shishkin, Maria M Krasilnikova & Sergei M Mirkin
doi:10.1038/nsmb.1527
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.
Abstract - | Full Text - Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility | PDF (303 KB) - Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility | Supplementary information
