Volume 19 Issue 2, February 2012

Volume 19 Issue 2

Asymmetric dimethylation of histone H3 arginine 2 is known to repress transcription. Guccione and colleagues now report that symmetric dimethylation of the same residue recruits the coactivator complex component WDR5, keeping genes poised for transcription. Image by tunart from www.istockphoto.com. pp 136–144

News and Views

  • News & Views |

    The proteins that 'pump' neurotransmitters into neurons, clearing the synapse after a nerve impulse, are central players in coherent brain function and are targets of many psychotropic drugs. Two groups now endeavor to resolve a fundamental controversy about how these proteins work. The results shed new light on the controversy but do not end it.

    • Hyun-Ho Lim
    •  & Christopher Miller
  • News & Views |

    The Cbl family of RING finger ubiquitin ligases regulates signaling in many systems. Two new studies provide a structural basis for how phosphorylation of a specific tyrosine in the Cbl proteins enhances their ubiquitin ligase activity, giving insight into how ubiquitination by Cbl proteins is restricted to specific substrates.

    • Stephen C Kales
    • , Philip E Ryan
    •  & Stanley Lipkowitz
  • News & Views |

    A complex of PUF (named after founding members Pumilio and Fem-3 binding factor) and Argonaute proteins can stall translation elongation on bound mRNAs by interacting with eEF1A and inhibiting its GTPase activity.

    • Amy E Pasquinelli

Research Highlights


  • Article |

    Although the asymmetric dimethylation of histone H3R2 acts as a repressive mark, new studies reveal that symmetrically dimethylated H3R2 (H3R2me2s) is a functional histone mark in vivo. The RBBP7 co-repressor is excluded from binding H3R2me2s in favor of the coactivator WDR5, which poises euchromatic genes for transcription activation upon cell-cycle exit and differentiation.

    • Valentina Migliori
    • , Julius Müller
    • , Sameer Phalke
    • , Diana Low
    • , Marco Bezzi
    • , Wei Chuen Mok
    • , Sanjeeb Kumar Sahu
    • , Jayantha Gunaratne
    • , Paola Capasso
    • , Christian Bassi
    • , Valentina Cecatiello
    • , Ario De Marco
    • , Walter Blackstock
    • , Vladimir Kuznetsov
    • , Bruno Amati
    • , Marina Mapelli
    •  & Ernesto Guccione
  • Article |

    Small noncoding RNAs function together with Argonaute (Ago) proteins as part of RNA-induced silencing complexes (RISCs). New biochemical analyses have identified the N domain of human AGO2 as the initiator of small duplex RNA unwinding during RISC assembly, which is required for both slicer-dependent and slicer-independent unwinding mechanisms.

    • Pieter Bas Kwak
    •  & Yukihide Tomari
  • Article |

    HtrA proteins have chaperone and protease activities, but how they bind and fold their substrates is poorly understood. New cryo-EM analyses of a protease-defective bacterial DegQ mutant in complex with several different substrates provide a structural model of HtrA proteins in their chaperone mode.

    • Hélène Malet
    • , Flavia Canellas
    • , Justyna Sawa
    • , Jun Yan
    • , Konstantinos Thalassinos
    • , Michael Ehrmann
    • , Tim Clausen
    •  & Helen R Saibil
  • Article |

    KirBac channels are the bacterial homologs of mammalian inwardly rectifying potassium (Kir) channels. All available structures are closed at the helix bundle crossing, but the crystal structure of an open-state KirBac channel now indicates how opening of the primary activation gate may be physically coupled to a rotational twist in the cytoplasmic domain.

    • Vassiliy N Bavro
    • , Rita De Zorzi
    • , Matthias R Schmidt
    • , João R C Muniz
    • , Lejla Zubcevic
    • , Mark S P Sansom
    • , Catherine Vénien-Bryan
    •  & Stephen J Tucker
  • Article |

    The Fanconi anemia pathway is involved in the repair of DNA interstrand cross-links, but it is also involved in regulation of translesion synthesis (TLS). The protein FAAP20 is now identified as a subunit of the Fanconi anemia core complex. FAAP20 interacts with TLS DNA polymerase Rev1, stabilizing Rev1's association with PCNA and promoting DNA damage bypass.

    • Hyungjin Kim
    • , Kailin Yang
    • , Donniphat Dejsuphong
    •  & Alan D D'Andrea
  • Article |

    Protease phosphorylation has been reported to affect many signaling pathways connected to proteolytic activity, but the underlying mechanisms have not been clearly elucidated. Structural and biochemical analyses of the deubiquitinase DUBA reveal that phosphorylation is necessary for productive ubiquitin substrate recognition and for enzyme activity.

    • Oscar W Huang
    • , Xiaolei Ma
    • , JianPing Yin
    • , Jeremy Flinders
    • , Till Maurer
    • , Nobuhiko Kayagaki
    • , Qui Phung
    • , Ivan Bosanac
    • , David Arnott
    • , Vishva M Dixit
    • , Sarah G Hymowitz
    • , Melissa A Starovasnik
    •  & Andrea G Cochran
  • Article |

    PUF (Pumilio/FBF) RNA-binding proteins and Argonaute (Ago) miRNA-binding proteins regulate mRNAs post-transcriptionally, each acting through similar yet distinct mechanisms. New genetic and biochemical analyses demonstrate that PUF and Ago proteins also function together in complex with elongation factor eEF1A to repress translation elongation.

    • Kyle Friend
    • , Zachary T Campbell
    • , Amy Cooke
    • , Peggy Kroll-Conner
    • , Marvin P Wickens
    •  & Judith Kimble
  • Article |

    Cbl RING ubiquitin ligases regulate receptor tyrosine kinase signal transduction and are in turn regulated by phosphorylation in their linker helix regions. Structural and biochemical analysis now shows that phosphorylation of c-Cbl leads to the release of an autoinhibited conformation, enhancing E2 binding and promoting ubiquitination activity.

    • Hao Dou
    • , Lori Buetow
    • , Andreas Hock
    • , Gary J Sibbet
    • , Karen H Vousden
    •  & Danny T Huang
  • Article |

    The processivity of myosins and kinesins has been well studied, but how the dynein homodimer achieves continuous motion is unknown. Two-dimensional analysis of labeled, DNA-dimerized dynein demonstrates that dynein has an unusual stepping pattern and can alternate between stochastic- and tension-based stepping to achieve processivity.

    • Weihong Qiu
    • , Nathan D Derr
    • , Brian S Goodman
    • , Elizabeth Villa
    • , David Wu
    • , William Shih
    •  & Samara L Reck-Peterson
  • Article |

    RNF8 and RNF168 are E3 ligases that promote the ubiquitination of histones at sites of double-strand breaks. Now RNF8 is shown to form mainly Lys48-linked ubiquitin chains and to modify KU80 bound to DNA breaks, promoting its removal and completion of DNA repair by NHEJ.

    • Lin Feng
    •  & Junjie Chen
  • Article |

    Crystal structures of the bacterial LeuT Na+-substrate symporter have revealed one substrate molecule in an occluded, centrally located binding site, whereas subsequent studies identified a putative second substrate binding site. Now additional binding analyses demonstrate that the second substrate binding site can be obscured during the preparation of detergent-solubilized LeuT for crystallography, explaining the apparent discrepancy in the reported stoichiometry.

    • Matthias Quick
    • , Lei Shi
    • , Britta Zehnpfennig
    • , Harel Weinstein
    •  & Jonathan A Javitch
  • Article |

    Recent studies have called into question the extent to which crystal structures of LeuT solubilized in β-OG detergent micelles reflect functionally relevant states. Now crystal structures of LeuT in lipid bicelles—a more native membrane-like context—show LeuT–substrate complexes nearly identical to the previously reported ones, with a single substrate molecule in the primary binding site.

    • Hui Wang
    • , Johannes Elferich
    •  & Eric Gouaux
  • Article |

    The splicing factor SRSF1 is an oncoprotein that is upregulated in human tumors, including breast cancer tumors. New in vitro and in vivo analyses reveal SRSF1's ability to transform human mammary epithelial cells and promote mammary gland tumorigenesis in a mouse model by regulating apoptosis and proliferation and cooperating with Myc while also uncovering potential downstream therapeutic targets.

    • Olga Anczuków
    • , Avi Z Rosenberg
    • , Martin Akerman
    • , Shipra Das
    • , Lixing Zhan
    • , Rotem Karni
    • , Senthil K Muthuswamy
    •  & Adrian R Krainer
  • Article |

    The core Qβ replicase is comprised of Qβ virus–encoded RNA-dependent polymerase and bacterial host–derived EF-Tu and EF-Ts, but the functions of these translation factors in RNA polymerization have been unclear. Structural analysis of Qβ replicase during polymerization reveals that EF-Tu functions as a modulator to separate the growing RNA strand from the template, ensuring processivity of the complex.

    • Daijiro Takeshita
    •  & Kozo Tomita
  • Article |

    Quinol-dependent nitric oxide reductase (qNOR) catalyzes the reduction of nitric oxide, which is emitted by bacteria, to produce nitrous oxide—an ozone-depleting gas and potent greenhouse gas. The crystal structure of qNOR from Geobacillus stearothermophilus allows a structural comparison with other respiratory enzymes, revealing functionally important similarities and differences between anaerobic and aerobic respiration.

    • Yushi Matsumoto
    • , Takehiko Tosha
    • , Andrei V Pisliakov
    • , Tomoya Hino
    • , Hiroshi Sugimoto
    • , Shingo Nagano
    • , Yuji Sugita
    •  & Yoshitsugu Shiro
  • Article |

    Eukaryotic cells choose the pathway to repair DNA double-strand breaks according to the cell-cycle phase, with homologous recombination preferred during S and G2 phases. Now the direct interaction between CDK2 and the C-terminus of Mre11 is revealed and shown to be important for phosphorylation of CtIP.

    • Jeffrey Buis
    • , Trina Stoneham
    • , Elizabeth Spehalski
    •  & David O Ferguson
  • Article |

    Non-nucleoside inhibitors (NNRTIs) against HIV-1 reverse transcriptase (RT) are used clinically, but the mechanism by which they interfere with RT's activity is still unclear. The crystal structure of a ternary complex composed of RT, primer-template DNA and NNRTI nevirapine now reveals that binding of the drug shifts the primer 3′ end from the active site, preventing nucleotide incorporation.

    • Kalyan Das
    • , Sergio E Martinez
    • , Joseph D Bauman
    •  & Eddy Arnold

Brief Communication

  • Brief Communication |

    Nuclear chromodomain-containing proteins read the epigenetic code by recognizing methylated lysine residues in histone tails. Structural analysis of the cytoplasmic chloroplast signal recognition particle subunit cpSRP34 in complex with the cpSRP54 subunit C-terminal tail comprising an arginine-rich motif reveals that a twinned aromatic cage reads two neighboring nonmethylated arginine residues and adapts chromodomains to a function outside the nucleus.

    • Iris Holdermann
    • , N Helge Meyer
    • , Adam Round
    • , Klemens Wild
    • , Michael Sattler
    •  & Irmgard Sinning