Volume 19 Issue 4, April 2012

Volume 19 Issue 4

Karlseder and colleagues show that prolonged mitotic arrest leads to telomere deprotection, triggering the DNA damage response and resulting in cell-cycle arrest or cell death. Taxol, the mitosis inhibitor used in some cancer treatments, is isolated from the bark of the Pacific Yew (Taxus brevifolia) shown here. Cover art by Erin Dewalt. pp 387–394

News and Views

Research Highlights

Review

  • Review Article |

    PrPSc, the infective agent for transmissible spongiform encephalopathies, is the misfolded form of the prion protein that can template the conversion of the native fold of the protein (PrPC). The high-resolution structure of PrPSc remains elusive. This review presents recent progress in the area and existing structural models, in addition to discussing the challenges ahead.

    • Rodrigo Diaz-Espinoza
    •  & Claudio Soto

Articles

  • Article |

    The ASAP complex is emerging as an assembly of proteins at the interface between transcription, pre-mRNA splicing and mRNA quality control. Structural analysis of the ASAP core complex reveals macromolecular interactions between the subunits and their assembly into ASAP. In addition, ASAP subunits SAP18 and RNPS1 are shown to bind Pinin, forming a novel complex called PSAP.

    • Andrea Giovanni Murachelli
    • , Judith Ebert
    • , Claire Basquin
    • , Hervé Le Hir
    •  & Elena Conti
  • Article |

    Mammalian telomeres are protected by shelterin components to avoid being recognized as DNA damage. Now cells under prolonged mitotic arrest are found to deprotect their telomeres, with dissociation of shelterin subunit TRF2 and degradation of the G-strand overhang. This leads to DNA damage signaling and checkpoint activation and apoptosis in the following G1 phase.

    • Makoto T Hayashi
    • , Anthony J Cesare
    • , James A J Fitzpatrick
    • , Eros Lazzerini-Denchi
    •  & Jan Karlseder
  • Article |

    TM287/288 is a heterodimeric ABC transporter found in Thermotoga maritima. The crystal structure of TM287/288 in the inward-facing AMP-PNP–bound state provides new insight into nucleotide binding by heterodimeric transporters and will serve as an important model for eukaryotic disease-associated homologs.

    • Michael Hohl
    • , Christophe Briand
    • , Markus G Grütter
    •  & Markus A Seeger
  • Article |

    Recruitment of elongation factor EF-G to the ribosome requires interaction between ribosomal proteins L12 and L11. New analyses identify a proline switch in L11, with the cis configuration allowing direct interaction between L11 and L12. EF-G has peptidyl-prolyl cis-trans isomerase activity driving the cis-trans isomerization of the proline switch, which might be a universal mechanism for efficient turnover of translational GTPases.

    • Li Wang
    • , Fang Yang
    • , Dejiu Zhang
    • , Zhi Chen
    • , Rui-Ming Xu
    • , Knud H Nierhaus
    • , Weimin Gong
    •  & Yan Qin
  • Article |

    Rhesus macaque TRIMCyp (RhTC) is a potent antiviral that inhibits the replication of diverse HIV viruses. New studies reveal that RhTC has evolved to become conformationally dynamic, and that RhTC can be engineered to switch from a single conformation that can target only HIV-1 to a dynamic state that can target multiple viral strains.

    • Matthew E C Caines
    • , Katsiaryna Bichel
    • , Amanda J Price
    • , William A McEwan
    • , Greg J Towers
    • , Brian J Willett
    • , Stefan M V Freund
    •  & Leo C James
  • Article |

    Topoisomerase 1 (Top1) inhibition is believed to mediate cellular toxicity by trapping Top1 on nicked DNA, leading to double-strand break formation during replication. New studies show that clinically relevant doses of Top1 poisons lead instead to extensive replication-fork reversal that is mediated by Poly(ADP-ribose) polymerases, limiting double-strand break formation.

    • Arnab Ray Chaudhuri
    • , Yoshitami Hashimoto
    • , Raquel Herrador
    • , Kai J Neelsen
    • , Daniele Fachinetti
    • , Rodrigo Bermejo
    • , Andrea Cocito
    • , Vincenzo Costanzo
    •  & Massimo Lopes
  • Article |

    Enterovirus 71 (EV71) is a major agent of hand, foot and mouth disease in children, but no vaccine or antiviral therapy is available. Structural analysis of the mature virus and natural empty particles reveals that the larger empty particles resemble elusive enterovirus uncoating intermediates, allowing insight into the process of enterovirus uncoating.

    • Xiangxi Wang
    • , Wei Peng
    • , Jingshan Ren
    • , Zhongyu Hu
    • , Jiwei Xu
    • , Zhiyong Lou
    • , Xumei Li
    • , Weidong Yin
    • , Xinliang Shen
    • , Claudine Porta
    • , Thomas S Walter
    • , Gwyndaf Evans
    • , Danny Axford
    • , Robin Owen
    • , David J Rowlands
    • , Junzhi Wang
    • , David I Stuart
    • , Elizabeth E Fry
    •  & Zihe Rao
  • Article |

    Zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses such as HIV-1 by targeting viral mRNA for degradation. Structural analysis now reveals a large RNA-binding surface comprising many positively charged residues and two cavities, thereby providing insight into how ZAP recognizes its target RNA.

    • Shoudeng Chen
    • , Yihui Xu
    • , Kuo Zhang
    • , Xinlu Wang
    • , Jian Sun
    • , Guangxia Gao
    •  & Yingfang Liu
  • Article |

    Current understanding of the structure of Dicer is restricted to simple forms of the enzyme from lower eukaryotes or isolated domains from higher eukaryotic Dicers. A new domain localization strategy was developed to determine the structure of human Dicer by EM, revealing the structural basis for small RNA production in eukaryotes.

    • Pick-Wei Lau
    • , Keelan Z Guiley
    • , Nabanita De
    • , Clinton S Potter
    • , Bridget Carragher
    •  & Ian J MacRae
  • Article |

    oskar mRNA localization to the posterior pole of the Drosophila melanogaster oocyte requires splicing of the first intron and the exon junction complex (EJC). In vitro and in vivo analyses demonstrate that splicing has a dual role in oskar mRNA localization by generating a secondary structural element required for RNP motility and depositing the EJC required for mRNA transport.

    • Sanjay Ghosh
    • , Virginie Marchand
    • , Imre Gáspár
    •  & Anne Ephrussi
  • Article |

    Archaeal initiation factor 2 (aIF2) in its GTP-bound form binds methionylated initiator tRNA to form a ternary initiation complex. Its 3D structure, as determined by crystallography and small-angle X-ray scattering analysis, reveals that despite the structural homology between aIF2 and elongation factor EF1A, these two G proteins of the translation apparatus use very different tRNA-binding strategies.

    • Emmanuelle Schmitt
    • , Michel Panvert
    • , Christine Lazennec-Schurdevin
    • , Pierre-Damien Coureux
    • , Javier Perez
    • , Andrew Thompson
    •  & Yves Mechulam

Brief Communications

  • Brief Communication |

    Interleukin-1 (IL-1) cytokines are important mediators of the innate and adaptive immune response. The structure of IL-1β bound to its receptor (IL-IR) and receptor accessory protein (IL-1RAcP) provides an important model for how these cytokines initiate signaling.

    • Christoph Thomas
    • , J Fernando Bazan
    •  & K Christopher Garcia
  • Brief Communication |

    SUMOylation targets HP1α to pericentric heterochromatin, but the enzyme responsible for removing the SUMO molecule from HP1α has not been determined. SENP7 is now identified as the factor that deconjugates SUMO, promoting retention of HP1α at these domains.

    • Christèle Maison
    • , Kelly Romeo
    • , Delphine Bailly
    • , Marion Dubarry
    • , Jean-Pierre Quivy
    •  & Geneviève Almouzni
  • Brief Communication |

    The crystal structure of the fusion protein from human metapneumovirus in complex with a potently neutralizing antibody reveals a novel antigenic site, which could be explored to develop vaccines against this and related paramyxoviruses.

    • Xiaolin Wen
    • , Jens C Krause
    • , George P Leser
    • , Reagan G Cox
    • , Robert A Lamb
    • , John V Williams
    • , James E Crowe Jr
    •  & Theodore S Jardetzky