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  • Structure of the neurotensin receptor 1 in complex with β-arrestin 1
    Nature (IF 43.070) Pub Date : 2020-01-16
    Weijiao Huang; Matthieu Masureel; Qu Qianhui; John Janetzko; Asuka Inoue; Hideaki E. Kato; Michael J. Robertson; Khanh C. Nguyen; Jeffrey S. Glenn; Georgios Skiniotis; Brian K. Kobilka

    Arrestin proteins bind to active, phosphorylated G-protein-coupled receptors (GPCRs), thereby preventing G-protein coupling, triggering receptor internalization, and affecting various downstream signalling pathways1,2. Although there is a wealth of structural information delineating the interactions between GPCRs and G proteins, less is known about how arrestins engage GPCRs. Here we report a cryo-EM structure of full-length human neurotensin receptor 1 (NTSR1) in complex with truncated human β-arrestin 1 (βarr1ΔCT). We found that phosphorylation of NTSR1 was critical for obtaining a stable complex with βarr1ΔCT, and identified phosphorylated sites in both the third intracellular loop and the C terminus that may promote this interaction. In addition, we observed a phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) molecule forming a bridge between the membrane side of NTSR1 transmembrane segments 1 and 4 and the C-lobe of arrestin. Compared to a structure of rhodopsin-arrestin-1, our structure displays an approximately 85° rotation of arrestin relative to the receptor. These findings highlight both conserved aspects but also the plasticity of arrestin–receptor interactions.

    更新日期:2020-01-17
  • Structure of the M2 muscarinic receptor–β-arrestin complex in a lipid nanodisc
    Nature (IF 43.070) Pub Date : 2020-01-16
    Dean P. Staus; Hongli Hu; Michael J. Robertson; Alissa L. W. Kleinhenz; Laura M. Wingler; William D. Capel; Naomi R. Latorraca; Robert J. Lefkowitz; Georgios Skiniotis

    Following agonist activation, G-protein-coupled receptors (GPCRs) recruit β-arrestin, which desensitizes heterotrimeric G-protein signalling and promotes receptor endocytosis1. Additionally, β-arrestin directly regulates many cell signalling pathways that can induce cellular responses distinct from that of G proteins2. Here we present a cryo-electron microscopy (cryo-EM) structure of β-arrestin 1 (βarr1) in complex with muscarinic acetylcholine-2-receptor (M2R) reconstituted in lipid nanodiscs. The M2R–βarr1 structure shows a multimodal network of flexible interactions, including binding of the βarr1 N domain to phosphorylated receptor residues and βarr1 finger loop insertion into the M2R seven-transmembrane bundle, which adopts a conformation similar to that in the M2R-heterotrimeric Go protein structure3. Moreover, the cryoEM map reveals that the βarr1 C-domain edge engages the lipid bilayer. Through atomistic simulations, biophysical, biochemical, and cellular assays, we show that the C-edge is critical for stable complex formation, βarr1 recruitment, receptor internalization, and desensitization of G-protein activation. Taken together, these data suggest the cooperative interactions of β-arrestin with both the receptor and phospholipid bilayer contribute to its functional versatility.

    更新日期:2020-01-17
  • Synthesis of rare sugar isomers through site-selective epimerization
    Nature (IF 43.070) Pub Date : 2020-01-15
    Yong Wang; Hayden M. Carder; Alison E. Wendlandt

    Glycans have diverse physiological functions, ranging from energy storage and structural integrity to cell signalling and the regulation of intracellular processes1. Although biomass-derived carbohydrates (such as (D)-glucose, (D)-xylose and (D)-galactose) are extracted on commercial scales, and serve as renewable chemical feedstocks and building blocks2,3, there are many hundreds of distinct monosaccharides that typically cannot be isolated from their natural sources and must instead be prepared through multistep chemical or enzymatic syntheses4,5. These ‘rare’ sugars feature prominently in bioactive natural products and pharmaceuticals, including many FDA-approved antiviral, antibacterial, anti-cancer and cardiac drugs6,7. Here we report the preparation of rare sugar isomers directly from biomass carbohydrates through site-selective epimerization reactions. Mechanistic studies establish that these reactions proceed under kinetic control, through sequential steps of hydrogen atom abstraction and hydrogen atom donation mediated by two distinct catalysts. This synthetic strategy provides concise and potentially extensive access to this valuable class of natural compounds.

    更新日期:2020-01-17
  • A distributional code for value in dopamine-based reinforcement learning
    Nature (IF 43.070) Pub Date : 2020-01-15
    Will Dabney; Zeb Kurth-Nelson; Naoshige Uchida; Clara Kwon Starkweather; Demis Hassabis; Rémi Munos; Matthew Botvinick
    更新日期:2020-01-16
  • Transparent ferroelectric crystals with ultrahigh piezoelectricity
    Nature (IF 43.070) Pub Date : 2020-01-15
    Chaorui Qiu; Bo Wang; Nan Zhang; Shujun Zhang; Jinfeng Liu; David Walker; Yu Wang; Hao Tian; Thomas R. Shrout; Zhuo Xu; Long-Qing Chen; Fei Li
    更新日期:2020-01-16
  • Signatures of self-organized criticality in an ultracold atomic gas
    Nature (IF 43.070) Pub Date : 2020-01-15
    S. Helmrich; A. Arias; G. Lochead; T. M. Wintermantel; M. Buchhold; S. Diehl; S. Whitlock
    更新日期:2020-01-16
  • Host-mediated ubiquitination of a mycobacterial protein suppresses immunity
    Nature (IF 43.070) Pub Date : 2020-01-15
    Lin Wang; Juehui Wu; Jun Li; Hua Yang; Tianqi Tang; Haijiao Liang; Mianyong Zuo; Jie Wang; Haipeng Liu; Feng Liu; Jianxia Chen; Zhonghua Liu; Yang Wang; Cheng Peng; Xiangyang Wu; Ruijuan Zheng; Xiaochen Huang; Yajun Ran; Zihe Rao; Baoxue Ge
    更新日期:2020-01-16
  • B cells and tertiary lymphoid structures promote immunotherapy response
    Nature (IF 43.070) Pub Date : 2020-01-15
    Beth A. Helmink; Sangeetha M. Reddy; Jianjun Gao; Shaojun Zhang; Rafet Basar; Rohit Thakur; Keren Yizhak; Moshe Sade-Feldman; Jorge Blando; Guangchun Han; Vancheswaran Gopalakrishnan; Yuanxin Xi; Hao Zhao; Rodabe N. Amaria; Hussein A. Tawbi; Alex P. Cogdill; Wenbin Liu; Valerie S. LeBleu; Fernanda G. Kugeratski; Sapna Patel; Michael A. Davies; Patrick Hwu; Jeffrey E. Lee; Jeffrey E. Gershenwald; Anthony Lucci; Reetakshi Arora; Scott Woodman; Emily Z. Keung; Pierre-Olivier Gaudreau; Alexandre Reuben; Christine N. Spencer; Elizabeth M. Burton; Lauren E. Haydu; Alexander J. Lazar; Roberta Zapassodi; Courtney W. Hudgens; Deborah A. Ledesma; SuFey Ong; Michael Bailey; Sarah Warren; Disha Rao; Oscar Krijgsman; Elisa A. Rozeman; Daniel Peeper; Christian U. Blank; Ton N. Schumacher; Lisa H. Butterfield; Monika A. Zelazowska; Kevin M. McBride; Raghu Kalluri; James Allison; Florent Petitprez; Wolf Herman Fridman; Catherine Sautès-Fridman; Nir Hacohen; Katayoun Rezvani; Padmanee Sharma; Michael T. Tetzlaff; Linghua Wang; Jennifer A. Wargo
    更新日期:2020-01-16
  • Antagonistic cooperativity between crystal growth modifiers
    Nature (IF 43.070) Pub Date : 2020-01-15
    Wenchuan Ma; James F. Lutsko; Jeffrey D. Rimer; Peter G. Vekilov
    更新日期:2020-01-16
  • Direct thermal neutron detection by the 2D semiconductor 6 LiInP 2 Se 6
    Nature (IF 43.070) Pub Date : 2020-01-15
    Daniel G. Chica; Yihui He; Kyle M. McCall; Duck Young Chung; Rahmi O. Pak; Giancarlo Trimarchi; Zhifu Liu; Patrick M. De Lurgio; Bruce W. Wessels; Mercouri G. Kanatzidis
    更新日期:2020-01-16
  • B cells are associated with survival and immunotherapy response in sarcoma
    Nature (IF 43.070) Pub Date : 2020-01-15
    Florent Petitprez; Aurélien de Reyniès; Emily Z. Keung; Tom Wei-Wu Chen; Cheng-Ming Sun; Julien Calderaro; Yung-Ming Jeng; Li-Ping Hsiao; Laetitia Lacroix; Antoine Bougoüin; Marco Moreira; Guillaume Lacroix; Ivo Natario; Julien Adam; Carlo Lucchesi; Yec′han Laizet; Maud Toulmonde; Melissa A. Burgess; Vanessa Bolejack; Denise Reinke; Khalid M. Wani; Wei-Lien Wang; Alexander J. Lazar; Christina L. Roland; Jennifer A. Wargo; Antoine Italiano; Catherine Sautès-Fridman; Hussein A. Tawbi; Wolf H. Fridman
    更新日期:2020-01-16
  • Archimedean lattices emerge in template-directed eutectic solidification
    Nature (IF 43.070) Pub Date : 2020-01-15
    Ashish A. Kulkarni; Erik Hanson; Runyu Zhang; Katsuyo Thornton; Paul V. Braun
    更新日期:2020-01-16
  • VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours
    Nature (IF 43.070) Pub Date : 2020-01-15
    Eric Song; Tianyang Mao; Huiping Dong; Ligia Simoes Braga Boisserand; Salli Antila; Marcus Bosenberg; Kari Alitalo; Jean-Leon Thomas; Akiko Iwasaki
    更新日期:2020-01-16
  • An anti-CRISPR viral ring nuclease subverts type III CRISPR immunity
    Nature (IF 43.070) Pub Date : 2020-01-15
    Januka S. Athukoralage; Stephen A. McMahon; Changyi Zhang; Sabine Grüschow; Shirley Graham; Mart Krupovic; Rachel J. Whitaker; Tracey M. Gloster; Malcolm F. White
    更新日期:2020-01-16
  • Isolation of an archaeon at the prokaryote–eukaryote interface
    Nature (IF 43.070) Pub Date : 2020-01-15
    Hiroyuki Imachi; Masaru K. Nobu; Nozomi Nakahara; Yuki Morono; Miyuki Ogawara; Yoshihiro Takaki; Yoshinori Takano; Katsuyuki Uematsu; Tetsuro Ikuta; Motoo Ito; Yohei Matsui; Masayuki Miyazaki; Kazuyoshi Murata; Yumi Saito; Sanae Sakai; Chihong Song; Eiji Tasumi; Yuko Yamanaka; Takashi Yamaguchi; Yoichi Kamagata; Hideyuki Tamaki; Ken Takai
    更新日期:2020-01-16
  • A population of dust-enshrouded objects orbiting the Galactic black hole
    Nature (IF 43.070) Pub Date : 2020-01-15
    Anna Ciurlo; Randall D. Campbell; Mark R. Morris; Tuan Do; Andrea M. Ghez; Aurélien Hees; Breann N. Sitarski; Kelly Kosmo O’Neil; Devin S. Chu; Gregory D. Martinez; Smadar Naoz; Alexander P. Stephan
    更新日期:2020-01-16
  • Improved protein structure prediction using potentials from deep learning
    Nature (IF 43.070) Pub Date : 2020-01-15
    Andrew W. Senior; Richard Evans; John Jumper; James Kirkpatrick; Laurent Sifre; Tim Green; Chongli Qin; Augustin Žídek; Alexander W. R. Nelson; Alex Bridgland; Hugo Penedones; Stig Petersen; Karen Simonyan; Steve Crossan; Pushmeet Kohli; David T. Jones; David Silver; Koray Kavukcuoglu; Demis Hassabis
    更新日期:2020-01-16
  • Design and synthesis of multigrain nanocrystals via geometric misfit strain
    Nature (IF 43.070) Pub Date : 2020-01-15
    Myoung Hwan Oh; Min Gee Cho; Dong Young Chung; Inchul Park; Youngwook Paul Kwon; Colin Ophus; Dokyoon Kim; Min Gyu Kim; Beomgyun Jeong; X. Wendy Gu; Jinwoung Jo; Ji Mun Yoo; Jaeyoung Hong; Sara McMains; Kisuk Kang; Yung-Eun Sung; A. Paul Alivisatos; Taeghwan Hyeon
    更新日期:2020-01-16
  • Classification with a disordered dopant-atom network in silicon
    Nature (IF 43.070) Pub Date : 2020-01-15
    Tao Chen; Jeroen van Gelder; Bram van de Ven; Sergey V. Amitonov; Bram de Wilde; Hans-Christian Ruiz Euler; Hajo Broersma; Peter A. Bobbert; Floris A. Zwanenburg; Wilfred G. van der Wiel
    更新日期:2020-01-16
  • The arms race between bacteria and their phage foes
    Nature (IF 43.070) Pub Date : 2020-01-15
    Hannah G. Hampton; Bridget N. J. Watson; Peter C. Fineran
    更新日期:2020-01-16
  • Tertiary lymphoid structures improve immunotherapy and survival in melanoma
    Nature (IF 43.070) Pub Date : 2020-01-15
    Rita Cabrita; Martin Lauss; Adriana Sanna; Marco Donia; Mathilde Skaarup Larsen; Shamik Mitra; Iva Johansson; Bengt Phung; Katja Harbst; Johan Vallon-Christersson; Alison van Schoiack; Kristina Lövgren; Sarah Warren; Karin Jirström; Håkan Olsson; Kristian Pietras; Christian Ingvar; Karolin Isaksson; Dirk Schadendorf; Henrik Schmidt; Lars Bastholt; Ana Carneiro; Jennifer A. Wargo; Inge Marie Svane; Göran Jönsson
    更新日期:2020-01-16
  • Decoding the development of the human hippocampus
    Nature (IF 43.070) Pub Date : 2020-01-15
    Suijuan Zhong; Wenyu Ding; Le Sun; Yufeng Lu; Hao Dong; Xiaoying Fan; Zeyuan Liu; Ruiguo Chen; Shu Zhang; Qiang Ma; Fuchou Tang; Qian Wu; Xiaoqun Wang
    更新日期:2020-01-16
  • Fast two-qubit logic with holes in germanium
    Nature (IF 43.070) Pub Date : 2020-01-13
    N. W. Hendrickx; D. P. Franke; A. Sammak; G. Scappucci; M. Veldhorst
    更新日期:2020-01-14
  • In vitro characterization of the human segmentation clock
    Nature (IF 43.070) Pub Date : 2020-01-08
    Margarete Diaz-Cuadros; Daniel E. Wagner; Christoph Budjan; Alexis Hubaud; Oscar A. Tarazona; Sophia Donelly; Arthur Michaut; Ziad Al Tanoury; Kumiko Yoshioka-Kobayashi; Yusuke Niino; Ryoichiro Kageyama; Atsushi Miyawaki; Jonathan Touboul; Olivier Pourquié
    更新日期:2020-01-09
  • Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition
    Nature (IF 43.070) Pub Date : 2020-01-08
    Jenny Y. Xue; Yulei Zhao; Jordan Aronowitz; Trang T. Mai; Alberto Vides; Besnik Qeriqi; Dongsung Kim; Chuanchuan Li; Elisa de Stanchina; Linas Mazutis; Davide Risso; Piro Lito
    更新日期:2020-01-09
  • Strain engineering and epitaxial stabilization of halide perovskites
    Nature (IF 43.070) Pub Date : 2020-01-08
    Yimu Chen; Yusheng Lei; Yuheng Li; Yugang Yu; Jinze Cai; Ming-Hui Chiu; Rahul Rao; Yue Gu; Chunfeng Wang; Woojin Choi; Hongjie Hu; Chonghe Wang; Yang Li; Jiawei Song; Jingxin Zhang; Baiyan Qi; Muyang Lin; Zhuorui Zhang; Ahmad E. Islam; Benji Maruyama; Shadi Dayeh; Lain-Jong Li; Kesong Yang; Yu-Hwa Lo; Sheng Xu
    更新日期:2020-01-09
  • Proton-assisted growth of ultra-flat graphene films
    Nature (IF 43.070) Pub Date : 2020-01-08
    Guowen Yuan; Dongjing Lin; Yong Wang; Xianlei Huang; Wang Chen; Xuedong Xie; Junyu Zong; Qian-Qian Yuan; Hang Zheng; Di Wang; Jie Xu; Shao-Chun Li; Yi Zhang; Jian Sun; Xiaoxiang Xi; Libo Gao
    更新日期:2020-01-09
  • Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease
    Nature (IF 43.070) Pub Date : 2020-01-08
    David Gate; Naresha Saligrama; Olivia Leventhal; Andrew C. Yang; Michael S. Unger; Jinte Middeldorp; Kelly Chen; Benoit Lehallier; Divya Channappa; Mark B. De Los Santos; Alisha McBride; John Pluvinage; Fanny Elahi; Grace Kyin-Ye Tam; Yongha Kim; Michael Greicius; Anthony D. Wagner; Ludwig Aigner; Douglas R. Galasko; Mark M. Davis; Tony Wyss-Coray
    更新日期:2020-01-09
  • Coupling delay controls synchronized oscillation in the segmentation clock
    Nature (IF 43.070) Pub Date : 2020-01-08
    Kumiko Yoshioka-Kobayashi; Marina Matsumiya; Yusuke Niino; Akihiro Isomura; Hiroshi Kori; Atsushi Miyawaki; Ryoichiro Kageyama
    更新日期:2020-01-09
  • Activation of the GLP-1 receptor by a non-peptidic agonist
    Nature (IF 43.070) Pub Date : 2020-01-08
    Peishen Zhao; Yi-Lynn Liang; Matthew J. Belousoff; Giuseppe Deganutti; Madeleine M. Fletcher; Francis S. Willard; Michael G. Bell; Michael E. Christe; Kyle W. Sloop; Asuka Inoue; Tin T. Truong; Lachlan Clydesdale; Sebastian G. B. Furness; Arthur Christopoulos; Ming-Wei Wang; Laurence J. Miller; Christopher A. Reynolds; Radostin Danev; Patrick M. Sexton; Denise Wootten
    更新日期:2020-01-09
  • A brief history of human disease genetics
    Nature (IF 43.070) Pub Date : 2020-01-08
    Melina Claussnitzer; Judy H. Cho; Rory Collins; Nancy J. Cox; Emmanouil T. Dermitzakis; Matthew E. Hurles; Sekar Kathiresan; Eimear E. Kenny; Cecilia M. Lindgren; Daniel G. MacArthur; Kathryn N. North; Sharon E. Plon; Heidi L. Rehm; Neil Risch; Charles N. Rotimi; Jay Shendure; Nicole Soranzo; Mark I. McCarthy
    更新日期:2020-01-09
  • Microbiota-targeted maternal antibodies protect neonates from enteric infection
    Nature (IF 43.070) Pub Date : 2020-01-08
    Wen Zheng; Wenjing Zhao; Meng Wu; Xinyang Song; Florence Caro; Ximei Sun; Francesca Gazzaniga; Giuseppe Stefanetti; Sungwhan Oh; John J. Mekalanos; Dennis L. Kasper
    更新日期:2020-01-09
  • Palaeoclimate evidence of vulnerable permafrost during times of low sea ice
    Nature (IF 43.070) Pub Date : 2020-01-08
    A. Vaks; A. J. Mason; S. F. M. Breitenbach; A. M. Kononov; A. V. Osinzev; M. Rosensaft; A. Borshevsky; O. S. Gutareva; G. M. Henderson
    更新日期:2020-01-09
  • The emergence of transcriptional identity in somatosensory neurons
    Nature (IF 43.070) Pub Date : 2020-01-08
    Nikhil Sharma; Kali Flaherty; Karina Lezgiyeva; Daniel E. Wagner; Allon M. Klein; David D. Ginty
    更新日期:2020-01-09
  • Nearest neighbours reveal fast and slow components of motor learning
    Nature (IF 43.070) Pub Date : 2020-01-08
    Sepp Kollmorgen; Richard H. R. Hahnloser; Valerio Mante
    更新日期:2020-01-09
  • Synthesis and properties of free-standing monolayer amorphous carbon
    Nature (IF 43.070) Pub Date : 2020-01-08
    Chee-Tat Toh; Hongji Zhang; Junhao Lin; Alexander S. Mayorov; Yun-Peng Wang; Carlo M. Orofeo; Darim Badur Ferry; Henrik Andersen; Nurbek Kakenov; Zenglong Guo; Irfan Haider Abidi; Hunter Sims; Kazu Suenaga; Sokrates T. Pantelides; Barbaros Özyilmaz
    更新日期:2020-01-09
  • Ocean acidification does not impair the behaviour of coral reef fishes
    Nature (IF 43.070) Pub Date : 2020-01-08
    Timothy D. Clark; Graham D. Raby; Dominique G. Roche; Sandra A. Binning; Ben Speers-Roesch; Fredrik Jutfelt; Josefin Sundin
    更新日期:2020-01-09
  • Single-chain heteropolymers transport protons selectively and rapidly
    Nature (IF 43.070) Pub Date : 2020-01-08
    Tao Jiang; Aaron Hall; Marco Eres; Zahra Hemmatian; Baofu Qiao; Yun Zhou; Zhiyuan Ruan; Andrew D. Couse; William T. Heller; Haiyan Huang; Monica Olvera de la Cruz; Marco Rolandi; Ting Xu
    更新日期:2020-01-09
  • 更新日期:2020-01-09
  • TGF-β orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1
    Nature (IF 43.070) Pub Date : 2020-01-08
    Jie Su; Sophie M. Morgani; Charles J. David; Qiong Wang; Ekrem Emrah Er; Yun-Han Huang; Harihar Basnet; Yilong Zou; Weiping Shu; Rajesh K. Soni; Ronald C. Hendrickson; Anna-Katerina Hadjantonakis; Joan Massagué
    更新日期:2020-01-09
  • A Galactic-scale gas wave in the solar neighborhood
    Nature (IF 43.070) Pub Date : 2020-01-07
    João Alves; Catherine Zucker; Alyssa A. Goodman; Joshua S. Speagle; Stefan Meingast; Thomas Robitaille; Douglas P. Finkbeiner; Edward F. Schlafly; Gregory M. Green

    For the past 150 years, the prevailing view of the local interstellar medium was based on a peculiarity known as Gould’s Belt1–4, an expanding ring of young stars, gas and dust, tilted about 20 degrees to the Galactic plane. Still, the physical relation between local gas clouds has remained practically unknown because the distance accuracy to clouds is of the same order as, or larger than, their sizes5–7. With the advent of large photometric surveys8 and astrometric survey9 this situation has changed10. Here we report the three-dimensional structure of all local cloud complexes. We find a narrow and coherent 2.7-kiloparsec arrangement of dense gas in the solar neighbourhood that contains many of the clouds thought to be associated with the Gould Belt. This finding is inconsistent with the notion that these clouds are part of a ring, disputing the Gould Belt model. The new structure comprises the majority of nearby star-forming regions, has an aspect ratio of about 1:20, and contains about three million solar masses of gas. Remarkably, the new structure appears to be undulating and its three-dimensional structure is well described by a damped sinusoidal wave on the plane of the Milky Way, with an average period of about 2 kiloparsecs and a maximum amplitude of about 160 parsecs.

    更新日期:2020-01-07
  • A repeating fast radio burst source localized to a nearby spiral galaxy
    Nature (IF 43.070) Pub Date : 2020-01-06
    B. Marcote; K. Nimmo; J. W. T. Hessels; S. P. Tendulkar; C. G. Bassa; Z. Paragi; A. Keimpema; M. Bhardwaj; R. Karuppusamy; V. M. Kaspi; C. J. Law; D. Michilli; K. Aggarwal; B. Andersen; A. M. Archibald; K. Bandura; G. C. Bower; P. J. Boyle; C. Brar; S. Burke-Spolaor; B. J. Butler; T. Cassanelli; P. Chawla; P. Demorest; M. Dobbs; E. Fonseca; U. Giri; D. C. Good; K. Gourdji; A. Josephy; A. Yu. Kirichenko; F. Kirsten; T. L. Landecker; D. Lang; T. J. W. Lazio; D. Z. Li; H.-H. Lin; J. D. Linford; K. Masui; J. Mena-Parra; A. Naidu; C. Ng; C. Patel; U.-L. Pen; Z. Pleunis; M. Rafiei-Ravandi; M. Rahman; A. Renard; P. Scholz; S. R. Siegel; K. M. Smith; I. H. Stairs; K. Vanderlinde; A. V. Zwaniga
    更新日期:2020-01-06
  • The structural basis for cohesin–CTCF-anchored loops
    Nature (IF 43.070) Pub Date : 2020-01-06
    Yan Li; Judith H. I. Haarhuis; Ángela Sedeño Cacciatore; Roel Oldenkamp; Marjon S. van Ruiten; Laureen Willems; Hans Teunissen; Kyle W. Muir; Elzo de Wit; Benjamin D. Rowland; Daniel Panne

    Cohesin catalyses the folding of the genome into loops that are anchored by CTCF1. The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2-SCC1 subunits of cohesin. A 2.6 Å crystal structure of SA2-SCC1 in complex with CTCF reveals the molecular basis of the interaction. We demonstrate that this interaction is specifically required for CTCF-anchored loops and contributes to the positioning of cohesin at CTCF-binding sites. A similar motif is present in a number of established and novel cohesin ligands, including the cohesin release factor WAPL2,3. Our data suggest that CTCF enables chromatin loop formation by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables dynamic regulation of chromatin folding by cohesin and CTCF.

    更新日期:2020-01-06
  • International evaluation of an AI system for breast cancer screening
    Nature (IF 43.070) Pub Date : 2020-01-01
    Scott Mayer McKinney; Marcin Sieniek; Varun Godbole; Jonathan Godwin; Natasha Antropova; Hutan Ashrafian; Trevor Back; Mary Chesus; Greg C. Corrado; Ara Darzi; Mozziyar Etemadi; Florencia Garcia-Vicente; Fiona J. Gilbert; Mark Halling-Brown; Demis Hassabis; Sunny Jansen; Alan Karthikesalingam; Christopher J. Kelly; Dominic King; Joseph R. Ledsam; David Melnick; Hormuz Mostofi; Lily Peng; Joshua Jay Reicher; Bernardino Romera-Paredes; Richard Sidebottom; Mustafa Suleyman; Daniel Tse; Kenneth C. Young; Jeffrey De Fauw; Shravya Shetty
    更新日期:2020-01-02
  • Inverse transition of labyrinthine domain patterns in ferroelectric thin films
    Nature (IF 43.070) Pub Date : 2020-01-01
    Y. Nahas; S. Prokhorenko; J. Fischer; B. Xu; C. Carrétéro; S. Prosandeev; M. Bibes; S. Fusil; B. Dkhil; V. Garcia; L. Bellaiche
    更新日期:2020-01-02
  • Spectroscopic confirmation of a mature galaxy cluster at a redshift of 2
    Nature (IF 43.070) Pub Date : 2020-01-01
    J. P. Willis; R. E. A. Canning; E. S. Noordeh; S. W. Allen; A. L. King; A. Mantz; R. G. Morris; S. A. Stanford; G. Brammer
    更新日期:2020-01-02
  • The past and future of global river ice
    Nature (IF 43.070) Pub Date : 2020-01-01
    Xiao Yang; Tamlin M. Pavelsky; George H. Allen
    更新日期:2020-01-02
  • Prevention of tuberculosis in macaques after intravenous BCG immunization
    Nature (IF 43.070) Pub Date : 2020-01-01
    Patricia A. Darrah; Joseph J. Zeppa; Pauline Maiello; Joshua A. Hackney; Marc H. Wadsworth; Travis K. Hughes; Supriya Pokkali; Phillip A. Swanson; Nicole L. Grant; Mark A. Rodgers; Megha Kamath; Chelsea M. Causgrove; Dominick J. Laddy; Aurelio Bonavia; Danilo Casimiro; Philana Ling Lin; Edwin Klein; Alexander G. White; Charles A. Scanga; Alex K. Shalek; Mario Roederer; JoAnne L. Flynn; Robert A. Seder
    更新日期:2020-01-02
  • Field-resolved infrared spectroscopy of biological systems
    Nature (IF 43.070) Pub Date : 2020-01-01
    Ioachim Pupeza; Marinus Huber; Michael Trubetskov; Wolfgang Schweinberger; Syed A. Hussain; Christina Hofer; Kilian Fritsch; Markus Poetzlberger; Lenard Vamos; Ernst Fill; Tatiana Amotchkina; Kosmas V. Kepesidis; Alexander Apolonski; Nicholas Karpowicz; Vladimir Pervak; Oleg Pronin; Frank Fleischmann; Abdallah Azzeer; Mihaela Žigman; Ferenc Krausz
    更新日期:2020-01-02
  • Assessing progress towards sustainable development over space and time
    Nature (IF 43.070) Pub Date : 2020-01-01
    Zhenci Xu; Sophia N. Chau; Xiuzhi Chen; Jian Zhang; Yingjie Li; Thomas Dietz; Jinyan Wang; Julie A. Winkler; Fan Fan; Baorong Huang; Shuxin Li; Shaohua Wu; Anna Herzberger; Ying Tang; Dequ Hong; Yunkai Li; Jianguo Liu
    更新日期:2020-01-02
  • Atomic imaging of the edge structure and growth of a two-dimensional hexagonal ice
    Nature (IF 43.070) Pub Date : 2020-01-01
    Runze Ma; Duanyun Cao; Chongqin Zhu; Ye Tian; Jinbo Peng; Jing Guo; Ji Chen; Xin-Zheng Li; Joseph S. Francisco; Xiao Cheng Zeng; Li-Mei Xu; En-Ge Wang; Ying Jiang
    更新日期:2020-01-02
  • GDF15 mediates the effects of metformin on body weight and energy balance
    Nature (IF 43.070) Pub Date : 2019-12-25
    Anthony P. Coll; Michael Chen; Pranali Taskar; Debra Rimmington; Satish Patel; John Tadross; Irene Cimino; Ming Yang; Paul Welsh; Samuel Virtue; Deborah A. Goldspink; Emily L. Miedzybrodzka; Adam R. Konopka; Raul Ruiz Esponda; Jeffrey T-J. Huang; Y. C. Loraine Tung; Sergio Rodriguez-Cuenca; Rute A. Tomaz; Heather P. Harding; Audrey Melvin; Giles S. H. Yeo; David Preiss; Antonio Vidal-Puig; Ludovic Vallier; K. Sreekumaran Nair; Nicholas J. Wareham; David Ron; Fiona M. Gribble; Frank Reimann; Naveed Sattar; David B. Savage; Bernard B. Allan; Stephen O’Rahilly

    Metformin, the world’s most prescribed anti-diabetic drug, is also effective in preventing type 2 diabetes in people at high risk1,2. Over 60% of this effect is attributable to the ability of metformin to lower body weight in a sustained manner3. The molecular mechanisms by which metformin lowers body weight are unknown. In two, independent randomised controlled clinical trials, circulating levels of GDF15, recently described to reduce food intake and lower body weight through a brain stem-restricted receptor, were increased by metformin. In wild-type mice, oral metformin increased circulating GDF15 with GDF15 expression increasing predominantly in the distal intestine and the kidney. Metformin prevented weight gain in response to a high-fat diet in wild-type mice but not in mice lacking GDF15 or its receptor GFRAL. In obese, high-fat-fed mice, the effects of metformin to reduce body weight were reversed by a GFRAL antagonist antibody. Metformin had effects on both energy intake and energy expenditure that required GDF15. Metformin retained its ability to lower circulating glucose levels in the absence of GDF15 action. In summary, metformin elevates circulating levels of GDF15, which are necessary for its beneficial effects on energy balance and body weight, major contributors to its action as a chemopreventive agent.

    更新日期:2019-12-26
  • Cortical pattern generation during dexterous movement is input-driven
    Nature (IF 43.070) Pub Date : 2019-12-25
    Britton A. Sauerbrei; Jian-Zhong Guo; Jeremy D. Cohen; Matteo Mischiati; Wendy Guo; Mayank Kabra; Nakul Verma; Brett Mensh; Kristin Branson; Adam W. Hantman
    更新日期:2019-12-26
  • A GPR174–CCL21 module imparts sexual dimorphism to humoral immunity
    Nature (IF 43.070) Pub Date : 2019-12-25
    Ruozhu Zhao; Xin Chen; Weiwei Ma; Jinyu Zhang; Jie Guo; Xiu Zhong; Jiacheng Yao; Jiahui Sun; Julian Rubinfien; Xuyu Zhou; Jianbin Wang; Hai Qi
    更新日期:2019-12-26
  • A sensory appendage protein protects malaria vectors from pyrethroids
    Nature (IF 43.070) Pub Date : 2019-12-25
    Victoria A. Ingham; Amalia Anthousi; Vassilis Douris; Nicholas J. Harding; Gareth Lycett; Marion Morris; John Vontas; Hilary Ranson
    更新日期:2019-12-26
  • H2A.Z facilitates licensing and activation of early replication origins
    Nature (IF 43.070) Pub Date : 2019-12-25
    Haizhen Long; Liwei Zhang; Mengjie Lv; Zengqi Wen; Wenhao Zhang; Xiulan Chen; Peitao Zhang; Tongqing Li; Luyuan Chang; Caiwei Jin; Guozhao Wu; Xi Wang; Fuquan Yang; Jianfeng Pei; Ping Chen; Raphael Margueron; Haiteng Deng; Mingzhao Zhu; Guohong Li
    更新日期:2019-12-26
  • Resonant microwave-mediated interactions between distant electron spins
    Nature (IF 43.070) Pub Date : 2019-12-25
    F. Borjans; X. G. Croot; X. Mi; M. J. Gullans; J. R. Petta
    更新日期:2019-12-26
  • Microbial bile acid metabolites modulate gut RORγ +  regulatory T cell homeostasis
    Nature (IF 43.070) Pub Date : 2019-12-25
    Xinyang Song; Ximei Sun; Sungwhan F. Oh; Meng Wu; Yanbo Zhang; Wen Zheng; Naama Geva-Zatorsky; Ray Jupp; Diane Mathis; Christophe Benoist; Dennis L. Kasper
    更新日期:2019-12-26
  • 更新日期:2019-12-26
  • Insights into the assembly and activation of the microtubule nucleator γ-TuRC
    Nature (IF 43.070) Pub Date : 2019-12-19
    Peng Liu; Erik Zupa; Annett Neuner; Anna Böhler; Justus Loerke; Dirk Flemming; Thomas Ruppert; Till Rudack; Christoph Peter; Christian Spahn; Oliver J. Gruss; Stefan Pfeffer; Elmar Schiebel

    Microtubules (MTs) are dynamic polymers of αβ-tubulin and play critical roles in cell signaling, cell migration, intracellular transport processes and chromosome segregation1. They assemble de novo from α/β-tubulin dimers in an essential process termed MT nucleation. Complexes containing the protein γ-tubulin serve as structural templates for the MT nucleation reaction2. In vertebrates, MTs are nucleated by the 2.2 MDa γ-tubulin ring complex (γ-TuRC) composed of γ-tubulin, five related γ-tubulin complex proteins (GCP2-6) and additional factors3. GCP6 is unique among the GCP proteins, because it carries an extended insertion domain of unknown function. High-resolution structural information on the γ-TuRC is not available, strongly limiting our understanding of MT formation in cells and tissue2. Here, we present the cryo-EM structure of γ-TuRC from Xenopus laevis at 4.8 Å global resolution, revealing a 14-spoked arrangement of GCPs and γ-tubulins in a partially flexible open left-handed spiral with a uniform sequence of GCP variants (Fig. 1a). Via specific interactions with other GCP proteins, the GCP6-specific insertion domain scaffolds the assembly of the γ-TuRC. Unexpectedly, we identified Actin as a bona fide structural component of γ-TuRC with functional relevance in MT nucleation. The γ-TuRC spiral geometry is suboptimal for MT nucleation and a controlled conformational rearrangement of the γ-TuRC is required for its activation. Collectively, our cryo-EM reconstruction provides unprecedented insights into the molecular organization, the assembly and the activation mechanism of vertebrate γ-TuRC and will serve as an important framework for the mechanistic understanding of fundamental biological processes associated with MT nucleation, e.g. meiotic and mitotic spindle formation and centriole biogensis4.

    更新日期:2019-12-19
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