Volume 22 Issue 3, March 2015

Volume 22 Issue 3

Crystallographic studies by Wang and colleagues reveal the structure of the bacterial vitamin C transporter UlaA and elucidate ascorbate binding and transport across the cell membrane. Cover image by © Iaroslav Danylchenko / Alamy. pp 238–241

Editorial

News and Views

  • News & Views |

    Mapping of ribonucleotides to single-nucleotide resolution in yeast genomes provides new insight into the enzymology of DNA replication.

    • Sue Jinks-Robertson
    •  & Hannah L Klein
  • News & Views |

    During infection, pathogenic Yersinia species secrete the antiphagocytic factor YopO (or YpkA), which contains a kinase domain and a Rho GTPase guanine nucleotide–dissociation inhibitor (GDI) domain. The structure of YopO in complex with actin, along with biochemical analyses, reveals the mechanism by which YopO uses actin to activate its kinase domain and recruit, phosphorylate and deactivate actin-assembly factors implicated in phagocytic clearance of the bacterium.

    • Roberto Dominguez
  • News & Views |

    Amyloids escape elimination by the proteasome, and their accumulation and subsequent aggregation contribute to various neurodegenerative conditions. A signature feature of amyloidogenic proteins is extended sequences rich in single amino acids. In this issue, Matouschek and colleagues now show that, to initiate degradation, the proteasome prefers substrates that have disordered regions with complex amino acid composition, thus indicating why it fails to rid the cell of most amyloids.

    • Matthew A Humbard
    •  & Michael R Maurizi

Research Highlights

Articles

  • Article |

    HydEn-seq, a new sequencing method that maps the distribution of ribonucleotides misincorporated by low-fidelity DNA polymerases in budding yeast, reveals unexpected strand-specific replication patterns in both nuclear and mitochondrial genomes.

    • Anders R Clausen
    • , Scott A Lujan
    • , Adam B Burkholder
    • , Clinton D Orebaugh
    • , Jessica S Williams
    • , Maryam F Clausen
    • , Ewa P Malc
    • , Piotr A Mieczkowski
    • , David C Fargo
    • , Duncan J Smith
    •  & Thomas A Kunkel
  • Article |

    Genome-wide DNA polymerase usage maps determined in fission yeast, using a new sequencing strategy based on ribonucleotide misincorporation, track the division of labor between replicative polymerases and reveal locations and efficiencies of replication origins.

    • Yasukazu Daigaku
    • , Andrea Keszthelyi
    • , Carolin A Müller
    • , Izumi Miyabe
    • , Tony Brooks
    • , Renata Retkute
    • , Mike Hubank
    • , Conrad A Nieduszynski
    •  & Antony M Carr
  • Article |

    The neuronal sorting receptor SorLA protects against Alzheimer's disease by binding Aβ peptides. Three new structures of the Vps10p Aβ-binding domain in ligand-free and ligand-bound forms explain the basis of SorLA peptide recognition.

    • Yu Kitago
    • , Masamichi Nagae
    • , Zenzaburo Nakata
    • , Maho Yagi-Utsumi
    • , Shizuka Takagi-Niidome
    • , Emiko Mihara
    • , Terukazu Nogi
    • , Koichi Kato
    •  & Junichi Takagi
  • Article |

    Aβ peptide aggregation is associated with Alzheimer's disease, and Aβ fibrils can catalyze formation of toxic oligomers. Molecular chaperone Brichos binds to the fibril surface, inhibiting the catalytic cycle in vitro, and limits Aβ toxicity.

    • Samuel I A Cohen
    • , Paolo Arosio
    • , Jenny Presto
    • , Firoz Roshan Kurudenkandy
    • , Henrik Biverstål
    • , Lisa Dolfe
    • , Christopher Dunning
    • , Xiaoting Yang
    • , Birgitta Frohm
    • , Michele Vendruscolo
    • , Jan Johansson
    • , Christopher M Dobson
    • , André Fisahn
    • , Tuomas P J Knowles
    •  & Sara Linse
  • Article |

    The proteasome initiates protein degradation at disordered regions within substrates. The proteasomal sequence preferences for the amino acid composition of these regions identified here affect protein half-life and explain unusual stability trends.

    • Susan Fishbain
    • , Tomonao Inobe
    • , Eitan Israeli
    • , Sreenivas Chavali
    • , Houqing Yu
    • , Grace Kago
    • , M Madan Babu
    •  & Andreas Matouschek
  • Article |

    Tumor-suppressor protein CYLD cleaves linear and Lys63-linked ubiquitin chains. Structures of CYLD USP domain with Met1- and Lys63-linked diubiquitins and biochemical analyses reveal the mechanism for dual specificity and provide insight into tumor-associated mutations.

    • Yusuke Sato
    • , Eiji Goto
    • , Yuri Shibata
    • , Yuji Kubota
    • , Atsushi Yamagata
    • , Sakurako Goto-Ito
    • , Keiko Kubota
    • , Jun-ichiro Inoue
    • , Mutsuhiro Takekawa
    • , Fuminori Tokunaga
    •  & Shuya Fukai
  • Article |

    Human DNA Polθ can mediate microhomology-mediated end-joining (MMEJ) of DNA molecules in cells and in vitro. Biochemistry work shows that Polθ promotes formation of DNA synapses and strand annealing, activities that require insertion loop 2.

    • Tatiana Kent
    • , Gurushankar Chandramouly
    • , Shane Michael McDevitt
    • , Ahmet Y Ozdemir
    •  & Richard T Pomerantz
  • Article |

    Crystal structures of the bacterial vitamin C transporter UlaA, a member of the AG family of the phosphoenolpyruvate-dependent phosphotransferase system, provide insights on binding to ascorbate and its transport across the cell membrane.

    • Ping Luo
    • , Xinzhe Yu
    • , Weiguang Wang
    • , Shilong Fan
    • , Xiaochun Li
    •  & Jiawei Wang
  • Article |

    New biochemical analyses in Xenopus cell-free extracts show that two replication forks must converge on a DNA interstrand cross-link (ICL) to permit translesion synthesis and repair.

    • Jieqiong Zhang
    • , James M Dewar
    • , Magda Budzowska
    • , Anna Motnenko
    • , Martin A Cohn
    •  & Johannes C Walter
  • Article |

    The identification of a new subclass of circular RNAs that are predominantly nuclear and promote transcription of their parental genes reveals a new regulatory function for these noncoding RNAs.

    • Zhaoyong Li
    • , Chuan Huang
    • , Chun Bao
    • , Liang Chen
    • , Mei Lin
    • , Xiaolin Wang
    • , Guolin Zhong
    • , Bin Yu
    • , Wanchen Hu
    • , Limin Dai
    • , Pengfei Zhu
    • , Zhaoxia Chang
    • , Qingfa Wu
    • , Yi Zhao
    • , Ya Jia
    • , Ping Xu
    • , Huijie Liu
    •  & Ge Shan

Brief Communications

  • Brief Communication |

    Serial femtosecond crystallography of the human δ-opioid receptor in complex with an endomorphin-derived peptide reveals interactions that are important for understanding the pharmacology of opioid peptides and developing analgesics with reduced side effects.

    • Gustavo Fenalti
    • , Nadia A Zatsepin
    • , Cecilia Betti
    • , Patrick Giguere
    • , Gye Won Han
    • , Andrii Ishchenko
    • , Wei Liu
    • , Karel Guillemyn
    • , Haitao Zhang
    • , Daniel James
    • , Dingjie Wang
    • , Uwe Weierstall
    • , John C H Spence
    • , Sébastien Boutet
    • , Marc Messerschmidt
    • , Garth J Williams
    • , Cornelius Gati
    • , Oleksandr M Yefanov
    • , Thomas A White
    • , Dominik Oberthuer
    • , Markus Metz
    • , Chun Hong Yoon
    • , Anton Barty
    • , Henry N Chapman
    • , Shibom Basu
    • , Jesse Coe
    • , Chelsie E Conrad
    • , Raimund Fromme
    • , Petra Fromme
    • , Dirk Tourwé
    • , Peter W Schiller
    • , Bryan L Roth
    • , Steven Ballet
    • , Vsevolod Katritch
    • , Raymond C Stevens
    •  & Vadim Cherezov

Corrigenda