Volume 22 Issue 2, February 2015

Volume 22 Issue 2

Structural studies by Lührmann, Pena and colleagues show how the RNA helicase Aquarius is recruited to the spliceosome, and reveal that Aquarius is positioned by a novel spliceosomal building block. The cover features the Aquarius constellation; cover design by Erin Dewalt based on photograph by Athos Boncompagni/iStock/Thinkstock. pp 138–144

News and Views

  • News & Views |

    Recognition of nucleic acids is a key strategy of the innate immune system to detect infectious organisms and tissue damage. Toll-like receptor (TLR) 8 was long assumed to be a receptor for single-stranded (ss) RNA. Unexpected findings now suggest that TLR8 recognizes RNA degradation products rather than ssRNA and that synergistic binding of two uridine-containing agonists at distinct sites of the receptor leads to activation of the innate immune response.

    • Matthias Geyer
    • , Karin Pelka
    •  & Eicke Latz
  • News & Views |

    Little is currently known about the molecular determinants of energy barriers along enzyme catalytic pathways. Kern and co-workers have studied this question in adenylate kinase (Adk) and now reveal that a single Mg2+ ion can accelerate two distinct steps, thus uncovering an unexpected dual role for this ubiquitous cofactor.

    • Anthony Mittermaier
  • News & Views |

    The structural rules governing the curving folds of solenoid proteins, as distilled down to the level of the underlying sequence repeats, provide designers with the tools to reliably fashion new variants with tunable geometries. Bespoke leucine-rich repeat (LRR) scaffolds, as recognition proteins, can now be tailored to better fit their targets.

    • J Fernando Bazan
    •  & Andrey V Kajava
  • News & Views |

    The ryanodine receptor (RyR), an ion channel regulating intracellular calcium release in excitable cells, has been challenging for structural analysis because of its colossal proportions compared to most other ion channels. Three independent groups have now used recent technological advancements in single-particle cryo-EM to make giant strides in solving the structure of this elusive protein complex.

    • Ivana Y Kuo
    •  & Barbara E Ehrlich

Research Highlights

Articles

  • Article |

    Toll-like receptors (TLRs) have key roles in innate immunity. Here, Shimizu and colleagues report crystal structures of TLR8 in complex with single-stranded RNA that reveal the molecular basis for recognition of a natural ligand.

    • Hiromi Tanji
    • , Umeharu Ohto
    • , Takuma Shibata
    • , Masato Taoka
    • , Yoshio Yamauchi
    • , Toshiaki Isobe
    • , Kensuke Miyake
    •  & Toshiyuki Shimizu
  • Article |

    Structural, computation and kinetics approaches reveal the energy landscape of catalysis by adenylate kinase and show that the cofactor Mg2+ activates two distinct molecular events in the reaction cycle: phosphoryl transfer and lid opening.

    • S Jordan Kerns
    • , Roman V Agafonov
    • , Young-Jin Cho
    • , Francesco Pontiggia
    • , Renee Otten
    • , Dimitar V Pachov
    • , Steffen Kutter
    • , Lien A Phung
    • , Padraig N Murphy
    • , Vu Thai
    • , Tom Alber
    • , Michael F Hagan
    •  & Dorothee Kern
  • Article |

    The γ-tubulin ring complex (γTuRC) nucleates microtubules in the cell. The functional, closed state of yeast γTuRC is now visualized, and its microtubule-nucleating activity is found to be species specific.

    • Justin M Kollman
    • , Charles H Greenberg
    • , Sam Li
    • , Michelle Moritz
    • , Alex Zelter
    • , Kimberly K Fong
    • , Jose-Jesus Fernandez
    • , Andrej Sali
    • , John Kilmartin
    • , Trisha N Davis
    •  & David A Agard
  • Article |

    Aquarius is an RNA helicase associated with spliceosomes. Lührmann, Pena and colleagues now provide structural insights into how Aquarius is recruited to the spliceosome, revealing a new spliceosomal building block that aids in Aquarius positioning.

    • Inessa De
    • , Sergey Bessonov
    • , Romina Hofele
    • , Karine dos Santos
    • , Cindy L Will
    • , Henning Urlaub
    • , Reinhard Lührmann
    •  & Vladimir Pena
  • Article |

    Proteins with charged amino acid residues encounter an electric force as they transit through membranes holding membrane potential. Von Heijne and colleagues measure this force to assess how membrane electrostatics contributes to translocation dynamics.

    • Nurzian Ismail
    • , Rickard Hedman
    • , Martin Lindén
    •  & Gunnar von Heijne
  • Article |

    CtIP helps maintain genomic stability by promoting DNA double-strand-break repair. Structural and biophysical analyses now show that the N terminus of human CtIP forms a tetrameric structure that is required for resection of broken DNA ends to permit their repair by homologous recombination.

    • Owen R Davies
    • , Josep V Forment
    • , Meidai Sun
    • , Rimma Belotserkovskaya
    • , Julia Coates
    • , Yaron Galanty
    • , Mukerrem Demir
    • , Christopher R Morton
    • , Neil J Rzechorzek
    • , Stephen P Jackson
    •  & Luca Pellegrini
  • Article |

    Structural, biophysical and genetic analyses reveal that Schizosaccharomyces pombe Ctp1 forms a flexible tetramer with multivalent DNA-binding and bridging activities that contribute to Ctp1's role in repair of DNA double-strand breaks.

    • Sara N Andres
    • , C Denise Appel
    • , James W Westmoreland
    • , Jessica S Williams
    • , Yvonne Nguyen
    • , Patrick D Robertson
    • , Michael A Resnick
    •  & R Scott Williams
  • Article |

    Leucine-rich repeats (LRRs) can form horseshoe-like structures with different curvatures in nature. A computational approach now allows the design of 12 new LRR proteins with precise curvatures, using defined building blocks and junction modules.

    • Keunwan Park
    • , Betty W Shen
    • , Fabio Parmeggiani
    • , Po-Ssu Huang
    • , Barry L Stoddard
    •  & David Baker