Brief Communications

  • Brief Communication |

    Crystal structure of the tubulin carboxypeptidase complex between vasohibin and SVBP, combined with mutagenesis, reveals the residues responsible for substrate recognition and cleavage.

    • Athanassios Adamopoulos
    • , Lisa Landskron
    • , Tatjana Heidebrecht
    • , Foteini Tsakou
    • , Onno B. Bleijerveld
    • , Maarten Altelaar
    • , Joppe Nieuwenhuis
    • , Patrick H. N. Celie
    • , Thijn R. Brummelkamp
    •  & Anastassis Perrakis
  • Brief Communication |

    MicroED structure of a peptide from the β2–α2 loop of the bank vole prion protein reveals a protofibril stabilized by a dense network of hydrogen bonds.

    • Marcus Gallagher-Jones
    • , Calina Glynn
    • , David R. Boyer
    • , Michael W. Martynowycz
    • , Evelyn Hernandez
    • , Jennifer Miao
    • , Chih-Te Zee
    • , Irina V. Novikova
    • , Lukasz Goldschmidt
    • , Heather T. McFarlane
    • , Gustavo F. Helguera
    • , James E. Evans
    • , Michael R. Sawaya
    • , Duilio Cascio
    • , David S. Eisenberg
    • , Tamir Gonen
    •  & Jose A. Rodriguez
  • Brief Communication |

    MILI-mediated piRNA processing and amplification is not essential for all MIWI2 male germline reprogramming activity, indicating the existence of a MILI-independent piRNA biogenesis pathway.

    • Lina Vasiliauskaitė
    • , Dimitrios Vitsios
    • , Rebecca V Berrens
    • , Claudia Carrieri
    • , Wolf Reik
    • , Anton J Enright
    •  & Dónal O'Carroll
  • Brief Communication |

    The crystal structure of full-length NS1 protein from Zika virus reveals an extended surface for membrane association and a highly variable polar surface.

    • W Clay Brown
    • , David L Akey
    • , Jamie R Konwerski
    • , Jeffrey T Tarrasch
    • , Georgios Skiniotis
    • , Richard J Kuhn
    •  & Janet L Smith
  • Brief Communication |

    The crystal structure of the phage anti-CRISPR protein AcrF3 in complex with Cas3 reveals its mode of inhibition of the CRISPR–Cas bacterial immune system.

    • Xiaofei Wang
    • , Deqiang Yao
    • , Jin-Gen Xu
    • , A-Rong Li
    • , Jianpo Xu
    • , Panhan Fu
    • , Yan Zhou
    •  & Yongqun Zhu
  • Brief Communication |

    Electron microscopy analyses of tethering complexes from different families, GARP and HOPS, show that they share a similar architecture featuring long flexible legs. The findings suggest that multisubunit tethering complexes use related structural frameworks to accomplish their functions.

    • Hui-Ting Chou
    • , Danijela Dukovski
    • , Melissa G Chambers
    • , Karin M Reinisch
    •  & Thomas Walz
  • Brief Communication |

    The complete architecture of the yeast COG tethering complex is revealed by negative-stain electron microscopy, showing an intricate shape with up to five flexible legs.

    • Jun Yong Ha
    • , Hui-Ting Chou
    • , Daniel Ungar
    • , Calvin K Yip
    • , Thomas Walz
    •  & Frederick M Hughson
  • Brief Communication |

    A crystal structure of the Zika virus NS3 RNA helicase reveals similarities to the RNA helicase from Dengue virus, with variability in loops typically involved in binding ATP and RNA, and aids in identification of potentially druggable hotspots.

    • Rinku Jain
    • , Javier Coloma
    • , Adolfo García-Sastre
    •  & Aneel K Aggarwal
  • Brief Communication |

    Probing the synthetic lethal effect of FANCD2 deletion in BRCA2-deficient cells reveals independent roles of FANCD2 and BRCA2 in stabilizing stalled replication forks to maintain genome stability and promote cell survival.

    • Johanna Michl
    • , Jutta Zimmer
    • , Francesca M Buffa
    • , Ultan McDermott
    •  & Madalena Tarsounas
  • Brief Communication |

    New crystal structures and supporting functional assays identify the p19 and p45 subunits of Tetrahymena telomerase as homologs of the Stn1 and Ten1 subunits of the CST complex, which coordinates telomere replication.

    • Bingbing Wan
    • , Ting Tang
    • , Heather Upton
    • , Jin Shuai
    • , Yuanzhe Zhou
    • , Song Li
    • , Juan Chen
    • , Joseph S Brunzelle
    • , Zhixiong Zeng
    • , Kathleen Collins
    • , Jian Wu
    •  & Ming Lei
  • Brief Communication |

    Flexible filamentous plant viruses, which cause substantial crop damage worldwide, have eluded structural characterization so far. The cryo-EM structure of BaMV now reveals the virus architecture and the structural basis of its flexibility.

    • Frank DiMaio
    • , Chun-Chieh Chen
    • , Xiong Yu
    • , Brandon Frenz
    • , Yau-Heiu Hsu
    • , Na-Sheng Lin
    •  & Edward H Egelman
  • Brief Communication |

    EM analyses reveal the architecture of cytoplasmic dynein in complex with dynactin and the BicD2 cargo adaptor on microtubules, showing the quaternary complex positioned for unidirectional movement and cargo recruitment.

    • Saikat Chowdhury
    • , Stephanie A Ketcham
    • , Trina A Schroer
    •  & Gabriel C Lander
  • 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
  • Brief Communication |

    PRC2 promotes methylation of H3K27, a modification that recruits PRC1, which in turn deposits H2A ubiquitin marks. Müller and colleagues use biochemistry approaches to show that H2Aub recruits Jarid–Aebp2–containing PRC2 to promote H3K27 trimethylation on H2Aub nucleosomes, thus forming a positive feedback loop to establish repressed chromatin domains.

    • Reinhard Kalb
    • , Sebastian Latwiel
    • , H Irem Baymaz
    • , Pascal W T C Jansen
    • , Christoph W Müller
    • , Michiel Vermeulen
    •  & Jürg Müller
  • Brief Communication |

    5'-adenylated DNA adducts generated during nucleotide excision repair (NER) are removed by aprataxin to permit DNA end ligation. Now, structural and kinetic analyses reveal that NER enzymes DNA polymerase β and FEN1 can also excise these adducts and thus provide a 'backup' repair pathway for abasic sites.

    • Melike Çağlayan
    • , Vinod K Batra
    • , Akira Sassa
    • , Rajendra Prasad
    •  & Samuel H Wilson
  • Brief Communication |

    Human endogenous retrovirus subfamily H (HERVH) is a class of transposable elements expressed preferentially in human embryonic stem cells (hESCs). A new study now shows that the long terminal repeats of HERVH function as enhancers and that HERVH is a nuclear long noncoding RNA required to maintain hESC identity.

    • Xinyi Lu
    • , Friedrich Sachs
    • , LeeAnn Ramsay
    • , Pierre-Étienne Jacques
    • , Jonathan Göke
    • , Guillaume Bourque
    •  & Huck-Hui Ng
  • Brief Communication |

    Using embryonic stem cells as a model system for studying the basic bimodal DNA methylation pattern in vivo, a new study now indicates that demethylation is not required for generating unmethylated regions such as CpG islands as part of the overall bimodal methylation pattern but is involved in resetting methylation patterns during somatic-cell reprogramming.

    • Ofra Sabag
    • , Ayelet Zamir
    • , Ilana Keshet
    • , Merav Hecht
    • , Guy Ludwig
    • , Amalia Tabib
    • , Joshua Moss
    •  & Howard Cedar
  • Brief Communication |

    The outer-membrane protein TamA is involved in autotransporter biogenesis in Escherichia coli. The crystal structure of TamA, determined to 2.3 Å, reveals a 16-strand β-barrel that is closed by a lid on its extracellular face. A weakened lateral wall in the barrel suggests the presence of a gate for substrate exit to the lipid bilayer.

    • Fabian Gruss
    • , Franziska Zähringer
    • , Roman P Jakob
    • , Björn M Burmann
    • , Sebastian Hiller
    •  & Timm Maier
  • Brief Communication |

    Archaeal glutamate transporter homologs catalyze the coupled uptake of aspartate and sodium ions. A new crystal structure of GltTk from Thermococcus kodakarensis shows the empty transporter oriented in the outward-facing conformation after substrate delivery, revealing how it is reset in preparation for another translocation cycle.

    • Sonja Jensen
    • , Albert Guskov
    • , Stephan Rempel
    • , Inga Hänelt
    •  & Dirk Jan Slotboom
  • Brief Communication |

    Equivalent mutations in the pseudokinase domain of Jak2 (V617F) and Jak1 (V658F) result in myeloproliferative disorders. Crystal structures of wild-type and the V658F mutant of human Jak1 spanning the pseudokinase domain and a segment of the SH2-PK linker now reveal the existence of a conformational switch that is stabilized by oncogenic mutations and favors activation.

    • Angela V Toms
    • , Anagha Deshpande
    • , Randall McNally
    • , Youngjee Jeong
    • , Julia M Rogers
    • , Chae Un Kim
    • , Sol M Gruner
    • , Scott B Ficarro
    • , Jarrod A Marto
    • , Martin Sattler
    • , James D Griffin
    •  & Michael J Eck
  • Brief Communication |

    Acetylation of the Sir3 N terminus is important for transcriptional silencing in budding yeast and is thought to promote binding of the Sir3 BAH domain to the nucleosome. Structural and biochemical analyses now demonstrate that the acetylated Sir3 N terminus does not interact with the nucleosome directly but instead stabilizes a nucleosome-binding loop in the BAH domain.

    • Dongxue Yang
    • , Qianglin Fang
    • , Mingzhu Wang
    • , Ren Ren
    • , Hong Wang
    • , Meng He
    • , Youwei Sun
    • , Na Yang
    •  & Rui-Ming Xu
  • Brief Communication |

    N-terminal acetylation of Sir3 is essential for heterochromatin establishment and maintenance in yeast, but its mechanism of action is unknown. The crystal structure of the N-terminally acetylated BAH domain of Sir3 bound to the nucleosome core particle revealed that N-terminal acetylation stabilizes the interaction of Sir3 with the nucleosome.

    • Nadia Arnaudo
    • , Israel S Fernández
    • , Stephen H McLaughlin
    • , Sew Y Peak-Chew
    • , Daniela Rhodes
    •  & Fabrizio Martino
  • Brief Communication |

    Initiation factors eIF1 and eIF1A are key determinants of ribosomal scanning and initiation-codon selection during translation initiation. The structure of Tetrahymena thermophila 40S ribosome in complex with eIF1 and eIF1A reveals the conformational changes that accompany initiation-factor binding and provides new insights into the mechanism of start-codon recognition.

    • Melanie Weisser
    • , Felix Voigts-Hoffmann
    • , Julius Rabl
    • , Marc Leibundgut
    •  & Nenad Ban
  • Brief Communication |

    Centromere protein A (CENP-A) is a histone H3 variant that specifies centromere location. Their reduced height relative to canonical H3 nucleosomes suggested that CENP-A nucleosomes might be tetrameric, but new biophysical measurements of reconstituted nucleosomes show that CENP-A confers a reduction in height on octameric CENP-A nucleosomes.

    • Matthew D D Miell
    • , Colin J Fuller
    • , Annika Guse
    • , Helena M Barysz
    • , Andrew Downes
    • , Tom Owen-Hughes
    • , Juri Rappsilber
    • , Aaron F Straight
    •  & Robin C Allshire
  • Brief Communication |

    The bacterial transporter XylE is a member of the major facilitator family (MFS). The structure of XylE in its partially occluded outward-facing state was recently solved. Now the same transporter is captured in different conformational states, inward open and partially occluded inward open, thus providing insights into the transport cycle of MFS transporters.

    • Esben M Quistgaard
    • , Christian Löw
    • , Per Moberg
    • , Lionel Trésaugues
    •  & Pär Nordlund
  • Brief Communication |

    Post-translational modifications of tRNAs can alter their decoding specificity. A molecular basis for altered codon specificity is now provided by the crystal structure of the archaeal tRNA2Ile modified with agmatidine at the wobble cytidine residue in complex with the AUA codon on the ribosome.

    • Rebecca M Voorhees
    • , Debabrata Mandal
    • , Cajetan Neubauer
    • , Caroline Köhrer
    • , Uttam L RajBhandary
    •  & V Ramakrishnan
  • Brief Communication |

    Adenosylcobalamin is a form of vitamin B12 that serves as a coenzyme in different reactions and as a ligand for riboswitches to control bacterial gene expression. The crystal structure of a B12 riboswitch from Symbiobacterium thermophilum bound to its ligand adenosylcobalamin is now presented, revealing the determinants for ligand recognition and gene expression control.

    • Alla Peselis
    •  & Alexander Serganov
  • Brief Communication |

    A systematic in vitro analysis of five different forms of cytosine in mammalian and yeast RNA polymerase II (Pol II) transcription demonstrates that Pol II can read and distinguish subtle differences in modified cytosines and process them differently, suggesting a putative functional interplay between cytosine modification status and transcription.

    • Matthew W Kellinger
    • , Chun-Xiao Song
    • , Jenny Chong
    • , Xing-Yu Lu
    • , Chuan He
    •  & Dong Wang
  • Brief Communication |

    The assembly of diverse immunoglobulin genes results in part from Rag protein–mediated DNA double-strand breaks at the edges of immunoglobulin gene segments, followed by the combinatorial reassembly of these segments. A transposase from the insect Helicoverpa zea is now shown to be active in vitro, and its breakage and joining activities resemble those of Rag, suggesting a common progenitor.

    • Cary G Hencken
    • , Xianghong Li
    •  & Nancy L Craig
  • Brief Communication |

    The crystal structures of human STING in the apo and c-di-GMP–bound states, supported by mutagenesis and biochemical data, reveal that c-di-GMP binds to preformed dimeric STING. c-di-GMP prolongs STING phosphorylation in vitro, which may contribute to downstream IFN signaling. These findings aid in understanding the innate immune response to bacterial infection.

    • Chang Shu
    • , Guanghui Yi
    • , Tylan Watts
    • , C Cheng Kao
    •  & Pingwei Li
  • Brief Communication |

    STING is an ER-resident membrane protein that triggers cytokine production upon detection of the bacterial second messenger c-di-GMP. The structures of the cytosolic domain of STING and the complex it forms with c-di-GMP lay the groundwork for understanding STING function.

    • Yi-He Huang
    • , Xiang-Yu Liu
    • , Xiao-Xia Du
    • , Zheng-Fan Jiang
    •  & Xiao-Dong Su
  • Brief Communication |

    STING is an important component of the innate immune system involved in the direct response to the bacterial second messenger c-di-GMP. The structures of human STING in the presence and absence of c-di-GMP show how recognition of c-di-GMP is achieved by dimeric STING, providing a basis for future studies investigating signal transduction mechanisms.

    • Guijun Shang
    • , Deyu Zhu
    • , Ning Li
    • , Junbing Zhang
    • , Chunyuan Zhu
    • , Defen Lu
    • , Cuilan Liu
    • , Qian Yu
    • , Yanyu Zhao
    • , Sujuan Xu
    •  & Lichuan Gu
  • Brief Communication |

    The process of pre-mRNA splicing involves connecting two exons while releasing the intron as a transient branched RNA, or as a lariat. Deep-sequencing analysis has enabled the first large-scale identification of branch points in human pre-mRNA transcripts in vivo, onto which the distribution of splicing factor binding was mapped.

    • Allison J Taggart
    • , Alec M DeSimone
    • , Janice S Shih
    • , Madeleine E Filloux
    •  & William G Fairbrother
  • Brief Communication |

    AMP-activated protein kinase (AMPK) has a central role in sensing cellular metabolic levels. Crystal structures of the AMPK core in the presence of AMP or ATP suggest that the third nucleotide-binding site in the γ subunit is important for allosteric regulation of kinase activity.

    • Lei Chen
    • , Jue Wang
    • , Yuan-Yuan Zhang
    • , S Frank Yan
    • , Dietbert Neumann
    • , Uwe Schlattner
    • , Zhi-Xin Wang
    •  & Jia-Wei Wu
  • Brief Communication |

    Poly ADP-ribosylation regulates cellular processes such as genomic stability maintenance, transcription and cell death. The structure of a mammalian poly(ADP-ribose) glycohydrolase gives insight into the enzyme's endoglycosidase activity and provides a basis for the development of therapeutic inhibitors.

    • In-Kwon Kim
    • , James R Kiefer
    • , Chris M W Ho
    • , Roderick A Stegeman
    • , Scott Classen
    • , John A Tainer
    •  & Tom Ellenberger
  • Brief Communication |

    Primary microRNA cleavage by the Microprocessor complex comprising Drosha and DGCR8 needs to be specific yet efficient. Mathematical modeling complemented with experimental analysis now shows that autoregulatory feedback on DGCR8 expression is crucial for balancing the efficiency and specificity of Microprocessor activity.

    • Omer Barad
    • , Mati Mann
    • , Elik Chapnik
    • , Archana Shenoy
    • , Robert Blelloch
    • , Naama Barkai
    •  & Eran Hornstein
  • Brief Communication |

    Group II introns, which are self-splicing catalytic RNAs, catalyze splicing in two distinct steps. The crystal structure of a group II intron in the pre-catalytic state directly preceding the first splicing step reveals a sharp kink in the backbone that presents the scissile phosphate of the splice site to the active site.

    • Russell T Chan
    • , Aaron R Robart
    • , Kanagalaghatta R Rajashankar
    • , Anna Marie Pyle
    •  & Navtej Toor
  • 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
  • Brief Communication |

    Numerous methylated residues exist on histone tails, the functional significance of which remains unknown. New studies in budding yeast now identify monomethylation of histone H4 lysine residues 5, 8 and 12 as functionally important marks that regulate cell growth and stress responses and are catalyzed by the first known H4 methyltransferase in budding yeast, Set5.

    • Erin M Green
    • , Gloria Mas
    • , Nicolas L Young
    • , Benjamin A Garcia
    •  & Or Gozani
  • Brief Communication |

    Some bacterial pathogens can obtain iron from the human host by extracting it from transferrin via two bacterial surface proteins, TfbA and TfbB. Now the crystal structures of Neisseria meningitidis TfbB in its apo state and bound to human transferrin reveal how TfbB sequesters transferrin and initiates iron release.

    • Charles Calmettes
    • , Joenel Alcantara
    • , Rong-Hua Yu
    • , Anthony B Schryvers
    •  & Trevor F Moraes
  • Brief Communication |

    Glutamate transporters couple the uptake of glutamate to the transport of cations. A new crystal structure of an archaeal trimeric glutamate transporter homolog, GltPh, captured in an intermediate conformation between the outward and inward facing states, provides insights into the transport mechanism.

    • Grégory Verdon
    •  & Olga Boudker