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Volume 455 Issue 7215, 16 October 2008

Channel hopping: protein translocation through the SecA–SecY complex Newly synthesized proteins are translocated across the eukaryotic endoplasmic reticulum membrane or the prokaryotic plasma membrane through an evolutionarily conserved protein conducting channel or translocon known as Sec61 in eukaryotes and SecY in prokaryotes. In bacteria, the SecA ATPase is thought to be the motor for translocation through the SecY channel. Two papers by Tom Rapoport and colleagues report the long-awaited structure of the SecA–SecY complex from bacteria. The structure, shown on the cover of this issuue, reveals major conformational changes between both partners and suggests that SecA uses a two-helix finger to push translocating proteins into SecY’s cytoplasmic funnel. Crosslinking studies provide further experimental support for this mechanism. In a third paper, Osamu Nureki and colleagues present a crystal structure of SecY bound to an anti-SecY Fab fragment revealing a pre-open state of the channel. Together these three papers provide novel insights into the path taken by a translocating protein. In News and Views, Anastassios Economou takes stock of where this work leaves current knowledge of this ‘astonishing cellular nanomachine’. [Article p. 936; Letters pp. 984, 988; News & Views p. 879]

Editorial

  • A congressional investigation alleges that some researchers have failed to report all the drug-company money that they have received — and that universities may have been too slow to police them.

    Editorial

    Advertisement

  • In an attempt to boost its struggling economy, Italy's government is focusing on easy, but unwise, targets.

    Editorial
  • Scientists need to ask themselves if their meeting or conference is really necessary.

    Editorial
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Research Highlights

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Journal Club

    • Andrzej Pietrzykowski
    Journal Club
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News

  • High-throughput gene sequencing seems to be stealing a march on microarrays. Heidi Ledford looks at a genome technology facing intense competition.

    • Heidi Ledford
    News
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News in Brief

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News Feature

  • In an effort to avoid a food crisis as the population grows, China is putting its weight behind genetically modified strains of the country's staple food crop. Jane Qiu explores the reasons for the unprecedented push.

    • Jane Qiu
    News Feature
  • The International Space Station's one chance of scientific greatness rests on a high-profile refugee from the world of the particle accelerator - but is it too long a shot to be worth taking? Eric Hand reports.

    • Eric Hand
    News Feature
  • Native Americans want to claim fossil resources found on their lands. Rex Dalton looks at how tribes and palaeontologists are working together to avoid bitter ownership disputes.

    • Rex Dalton
    News Feature
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Correspondence

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Autumn Books

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Essay

  • Why does a developing nation have such an ambitious space programme? Subhadra Menon traces its foundations back to the work of one visionary physicist 60 years ago.

    • Subhadra Menon
    Essay
  • The 1980s saw plenty of discussion on sequencing the human genome. But, according to Charles DeLisi, one conference was crucial for converting an idea to reality.

    • Charles DeLisi
    Essay
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News & Views

  • Precisely how proteins snake their way through channels in cell membranes is unclear. Complexes between the SecY channel and its motor protein, and the use of a 'molecular endoscope', provide fascinating clues.

    • Anastassios Economou
    News & Views
  • Observations of the birth of a superfluid have uncovered details of the microphysics of phase transitions. Whether these results can be used to model such transitions in the early Universe is an open question.

    • Kristian Helmerson
    News & Views
  • Increasingly sophisticated techniques are being used to persuade ancient rocks to yield information about conditions on and in the early Earth — for instance, about the oxidation state of the mantle.

    • William F. McDonough
    News & Views
  • The childhood cancer neuroblastoma can either run in families or occur sporadically. Several studies find that the gene ALK is a chief offender in this disease, because its germline mutations mediate both forms.

    • Charis Eng
    News & Views
  • A provocative contribution to the logic of science extends the theorems of Kurt Gödel and Alan Turing, and bears on thinking about prediction, the standard model of particles, and quantum gravity.

    • P.-M. Binder
    News & Views
  • Messenger RNAs don't usually correspond exactly to DNA — portions of the primary transcript, known as introns, are removed by splicing. A study reveals new ways in which splicing can be regulated.

    • Bruce Futcher
    • Janet K. Leatherwood
    News & Views
  • Mapping out the resonant modes of optical antennas is part of a largely unexplored terrain — but not any more, as a study that applies a luminescence technique to gold antennas demonstrates.

    • Lukas Novotny
    News & Views
  • Tiny, wind-generated ripples on the sea surface can interact and produce pressure changes felt on the ocean floor. The same line of study points to a basic distinction between two types of surface wave.

    • Steve Elgar
    News & Views
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Editorial

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Introduction

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Review Article

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Article

  • The Devonian fossil Tiktaalik roseae represents a transitional form between fishes and tetrapods. This paper presents a detailed examination of the braincase of this creature. Although primitive in many respects, some features nod to the tetrapod state.

    • Jason P. Downs
    • Edward B. Daeschler
    • Neil H. Shubin
    Article
  • ALK is identified as a neuroblastoma predisposition gene. Germline mutations were found in ALK, a tryrosine kinase receptor, in affected families. In addition, somatic point mutations in ALK were found in sporadic cases of neuroblastomas. ALK mutations seem to lead to constitutive activation of its kinase activity and promote cell proliferation.

    • Yaël P. Mossé
    • Marci Laudenslager
    • John M. Maris
    Article
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Letter

  • Clusters of galaxies are the largest gravitationally bound objects in the Universe. Magnetic fields and relativistic particles are mixed with the gas as revealed by giant 'radio haloes'. A radio halo at low frequencies associated with the merging cluster Abell 521 is reported. This halo has an extremely steep radio spectrum that makes it difficult to detect with observations at 1.4 GHz. The spectrum supports a turbulent acceleration mechanism, which predicts that many radio haloes in the Universe should emit mainly at low frequencies.

    • G. Brunetti
    • S. Giacintucci
    • M. Markevitch
    Letter
  • This paper presents an experimental and theoretical study of the Bose–Einstein condensation phase transition of a trapped atomic gas. The vortices formed spontaneously during condensation are observed and characterized, and the results provide further understanding of the development of coherence in superfluids.

    • Chad N. Weiler
    • Tyler W. Neely
    • Brian P. Anderson
    Letter
  • This paper reports the observation of quantum oscillations in the overdoped superconductor Tl2Ba2CuO6+δ that show the existence of a large Fermi surface of well-defined quasiparticles covering two-thirds of the Brillouin zone. These measurements firmly establish the applicability of a generalized Fermi-liquid picture on the overdoped side of the superconducting dome.

    • B. Vignolle
    • A. Carrington
    • N. E. Hussey
    Letter
  • An ambition in the field of organic electronics has been to harness the self-organizing properties of certain classes of molecules to assemble key device structures without human intervention. Single, self-assembled layers of such molecules have been successfully implemented in transistors, but the devices' properties have not been promising, largely due to defects in the monolayers and poor electronic coupling between the molecules within the layers. It is now shown how such limitations can be overcome, by carefully tuning the properties of the molecules through chemical design to ensure dense, highly ordered packing in the self-assembled monolayer. The good electrical performance and high reproducibility of the resulting devices is demonstrated by combining over 300 of them into a functional integrted circuit.

    • Edsger C. P. Smits
    • Simon G. J. Mathijssen
    • Dago M. de Leeuw
    Letter
  • The original iron isotope ratios of a 2.7 billion-year-old komatiitic magma from Belingwe, Zimbabwe have been determined. These measurements are consistent with near-anhydrous melting of a source with similar oxidation state to that of present-day ocean-floor basalt. The results support the identification of the Belingwe komatiite as a product of high mantle temperatures of 1,700 °C, rather than melting under hydrous conditions, confirming the existence of anomalously hot mantle in the Archean.

    • Andrew J. Berry
    • Leonid V. Danyushevsky
    • Stephen R. Sutton
    Letter
  • The evolution of cooperation between unrelated individuals is a puzzle that attracts interest both in the social and in the natural sciences. Theoretical concepts may fail to capture essential features of real life cooperation. This paper focuses on the cleaning mutualism between cleaner wrasse and their client fish. A game theoretical model predicts that two providers should offer a higher service quality to clients than single providers, as long as they cooperate among each other. Field observations and an experimental test confirm the model prediction.

    • Redouan Bshary
    • Alexandra S. Grutter
    • Olof Leimar
    Letter
  • This is one of four papers in this issue that identifies mutations in the tyrosine kinase receptor ALK in neuroblastoma, the most frequent childhood cancer. ALK is found to be a neuroblastoma predisposition gene and somatic points mutations were found in sporadic cases of neuroblastoma. These mutations lead the ALK kinase activation and are able to transform cells and display tumourigenic activity in vivo. ALK inhibitors decrease neuroblastoma cell proliferating and are potential anti-cancer drugs for the treatment of neuroblastoma.

    • Isabelle Janoueix-Lerosey
    • Delphine Lequin
    • Olivier Delattre
    Letter
  • This is one of four papers in this issue that identifies mutations in the tyrosine kinase receptor ALK in neuroblastoma, the most frequent childhood cancer. ALK is found to be a neuroblastoma predisposition gene and somatic points mutations were found in sporadic cases of neuroblastoma. These mutations lead the ALK kinase activation and are able to transform cells and display tumourigenic activity in vivo. ALK inhibitors decrease neuroblastoma cell proliferating and are potential anti-cancer drugs for the treatment of neuroblastoma.

    • Yuyan Chen
    • Junko Takita
    • Seishi Ogawa
    Letter
  • This is one of four papers in this issue that identifies mutations in the tyrosine kinase receptor ALK in neuroblastoma, the most frequent childhood cancer. ALK is found to be a neuroblastoma predisposition gene and somatic points mutations were found in sporadic cases of neuroblastoma. These mutations lead the ALK kinase activation and are able to transform cells and display tumourigenic activity in vivo. ALK inhibitors decrease neuroblastoma cell proliferating and are potential anti-cancer drugs for the treatment of neuroblastoma.

    • Rani E. George
    • Takaomi Sanda
    • A. Thomas Look
    Letter
  • A crystal structure of the human Hedgehog protein Shh complexed with the cell surface protein CDO reveals that the interaction involves a previously unrecognized calcium-binding site in Shh. The binding mode is quite different from the interaction between the Drosophila homologues of these proteins. Mutations in Shh causing congenital malformations map to the calcium-binding site and disrupt interactions with binding partners.

    • Jason S. McLellan
    • Xiaoyan Zheng
    • Daniel J. Leahy
    Letter
  • This is one of two papers that report the long-awaited structure of the SecA–SecY complex from bacteria. The structure reveals major conformational changes between both partners and suggests that SecA uses a two-helix finger to push translocating proteins inside the cytoplasmic funnel of SecY. Cross-linking studies provide further experimental support for this mechanism.

    • Karl J. Erlandson
    • Stephanie B. M. Miller
    • Tom A. Rapoport
    Letter
  • TRPML1 is a member of the Transient Receptor Potential (TRP) superfamily of ion channels, and mutation in the human TRPML1 gene causes mucolipidosis, symptoms of which include anaemia. It is shown that TRPML1 functions as a Fe2+-permeable channel in lysosomes, and that disease-associated mutations impair Fe2+transport, suggesting that impaired iron transport may underlie symptoms of mucolipidosis.

    • Xian-Ping Dong
    • Xiping Cheng
    • Haoxing Xu
    Letter
  • Rem1 expression is controlled not only at the level of transcription, but also by splicing. In mitotic cells, binding of the Fkh2 transcription factor to the rem1 promoter yields a transcript that retains its introns so that only a short protein is produced; this protein affects recombination levels. In meiotic cells, the binding of the meiosis-specific trancription factor Mei4 to the rem1 promoter results in splicing of rem1, yielding the cyclin isoform. Thus, this work demonstrates that two transcription factors can differentially affecting splicing of the same gene.

    • Alberto Moldón
    • Jordi Malapeira
    • José Ayté
    Letter
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Prospects

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Special Report

  • The demand for science skills in non-governmental organizations is rising. Paroma Basu, Jane Qiu and Kendall Powell report.

    • Paroma Basu
    • Jane Qiu
    • Kendall Powell
    Special Report
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Movers

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Networks and Support

  • Government looking for mix of talents to help assess fisheries.

    • Karen Kaplan
    Networks and Support
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Career View

  • Trying to team-up while working alone.

    • Jon Yearsley
    Career View
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Futures

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Authors

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Insight

  • Neuropsychiatric diseases, such as schizophrenia, depression and autism, are a huge burden on society, impairing the health of those affected, as well as their ability to learn and to work. After half a century of concerted effort, researchers are now making progress towards defining the biological basis of these diseases. Technological advances in the areas of genomics and large-scale studies, as well as the development of new animal models, are improving our understanding of these diseases and are offering the prospect of fundamentally different options for treatment.

    Insight
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