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Nature Structural & Molecular Biology

Minakshi Gandhi, Maiwen Caudron-Herger, Sven Diederichs
Although the number of documented noncoding RNAs (ncRNAs) is rapidly increasing, knowledge of their molecular function is lagging behind. The identification of specific RNA motifs that mediate transcript stability, interactions and localization may aid in the prediction of these features in new transcripts and may have potential implications for ncRNA function. Here, we review RNA motifs, focusing on four recent studies identifying nuclear-retention motifs, and discuss the limited specificity of short-RNA motifs and the resulting challenge for effective functional prediction...
November 12, 2018: Nature Structural & Molecular Biology
Kunrong Mei, Yan Li, Shaoxiao Wang, Guangcan Shao, Jia Wang, Yuehe Ding, Guangzuo Luo, Peng Yue, Jun-Jie Liu, Xinquan Wang, Meng-Qiu Dong, Hong-Wei Wang, Wei Guo
In the version of this article originally published, the value given for electron dose in Table 1 was incorrect. This value was originally stated as 4.8 but should have been 50. The error has been corrected in the HTML and PDF versions of the article.
November 5, 2018: Nature Structural & Molecular Biology
Johannes M Herrmann, Pedro Carvalho, Manajit Hayer-Hartl, Tohru Yoshihisa
No abstract text is available yet for this article.
October 29, 2018: Nature Structural & Molecular Biology
Blake A Caldwell, Marisa S Bartolomei
No abstract text is available yet for this article.
October 29, 2018: Nature Structural & Molecular Biology
Xiaoli Zhang, Meiqin Hu, Yexin Yang, Haoxing Xu
Mammalian transient receptor potential (TRP) channels mediate Ca2+ flux and voltage changes across membranes in response to environmental and cellular signals. At the plasma membrane, sensory TRPs act as neuronal detectors of physical and chemical environmental signals, and receptor-operated (metabotropic) TRPs decode extracellular neuroendocrine cues to control body homeostasis. In intracellular membranes, such as those in lysosomes, organellar TRPs respond to compartment-derived signals to control membrane trafficking, signal transduction, and organelle function...
October 29, 2018: Nature Structural & Molecular Biology
Francis J O'Reilly, Juri Rappsilber
Over the past decade, cross-linking mass spectrometry (CLMS) has developed into a robust and flexible tool that provides medium-resolution structural information. CLMS data provide a measure of the proximity of amino acid residues and thus offer information on the folds of proteins and the topology of their complexes. Here, we highlight notable successes of this technique as well as common pipelines. Novel CLMS applications, such as in-cell cross-linking, probing conformational changes and tertiary-structure determination, are now beginning to make contributions to molecular biology and the emerging fields of structural systems biology and interactomics...
October 29, 2018: Nature Structural & Molecular Biology
Tatsuaki Kurosaki, Keita Miyoshi, Jason R Myers, Lynne E Maquat
In the version of this paper originally published, in the PDF references 48-55 appeared in the reference list for the Methods section although they should have been in the reference list for the main text. The error has been corrected in the PDF now available.
October 23, 2018: Nature Structural & Molecular Biology
Felix J Kim, Gavril W Pasternak
No abstract text is available yet for this article.
October 11, 2018: Nature Structural & Molecular Biology
Scott Horowitz, Loïc Salmon, Philipp Koldewey, Logan S Ahlstrom, Raoul Martin, Shu Quan, Pavel V Afonine, Henry van den Bedem, Lili Wang, Qingping Xu, Raymond C Trievel, Charles L Brooks, James C A Bardwell
No abstract text is available yet for this article.
October 8, 2018: Nature Structural & Molecular Biology
Jimin Wang
No abstract text is available yet for this article.
October 8, 2018: Nature Structural & Molecular Biology
Dan Dominissini, Gideon Rechavi
No abstract text is available yet for this article.
September 28, 2018: Nature Structural & Molecular Biology
Qin Yang, Sven Brüschweiler, Linlin Zhao, James J Chou
No abstract text is available yet for this article.
September 3, 2018: Nature Structural & Molecular Biology
Enrique Marcos, Tamuka M Chidyausiku, Andrew C McShan, Thomas Evangelidis, Santrupti Nerli, Lauren Carter, Lucas G Nivón, Audrey Davis, Gustav Oberdorfer, Konstantinos Tripsianes, Nikolaos G Sgourakis, David Baker
β-sheet proteins carry out critical functions in biology, and hence are attractive scaffolds for computational protein design. Despite this potential, de novo design of all-β-sheet proteins from first principles lags far behind the design of all-α or mixed-αβ domains owing to their non-local nature and the tendency of exposed β-strand edges to aggregate. Through study of loops connecting unpaired β-strands (β-arches), we have identified a series of structural relationships between loop geometry, side chain directionality and β-strand length that arise from hydrogen bonding and packing constraints on regular β-sheet structures...
November 2018: Nature Structural & Molecular Biology
Roberto Vendramin, Yvessa Verheyden, Hideaki Ishikawa, Lucas Goedert, Emilien Nicolas, Kritika Saraf, Alexandros Armaos, Riccardo Delli Ponti, Keichi Izumikawa, Pieter Mestdagh, Denis L J Lafontaine, Gian Gaetano Tartaglia, Nobuhiro Takahashi, Jean-Christophe Marine, Eleonora Leucci
Synchronization of mitochondrial and cytoplasmic translation rates is critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to translational uncoupling. Although alterations of cytosolic protein synthesis are common in human cancer, compensating mechanisms in mitochondrial translation remain elusive. Here we show that the malignant long non-coding RNA (lncRNA) SAMMSON promotes a balanced increase in ribosomal RNA (rRNA) maturation and protein synthesis in the cytosol and mitochondria by modulating the localization of CARF, an RNA-binding protein that sequesters the exo-ribonuclease XRN2 in the nucleoplasm, which under normal circumstances limits nucleolar rRNA maturation...
November 2018: Nature Structural & Molecular Biology
Manqing Li, Elaine Kao, Dane Malone, Xia Gao, Jean Y J Wang, Michael David
Transcriptome analysis reveals a strong positive correlation between human Schlafen family member 11 (SLFN11) expression and the sensitivity of tumor cells to DNA-damaging agents (DDAs). Here, we show that SLFN11 preferentially inhibits translation of the serine/threonine kinases ATR and ATM upon DDA treatment based on distinct codon usage without disrupting early DNA damage response signaling. Type II transfer RNAs (tRNAs), which include all serine and leucine tRNAs, are cleaved in a SLFN11-dependent manner in response to DDAs...
November 2018: Nature Structural & Molecular Biology
Kai Zhang, Xiaorong Zhang, Zhiqiang Cai, Jie Zhou, Ran Cao, Ya Zhao, Zonggui Chen, Dehe Wang, Wen Ruan, Qian Zhao, Guangqiao Liu, Yuanchao Xue, Yan Qin, Bing Zhou, Ligang Wu, Timothy Nilsen, Yu Zhou, Xiang-Dong Fu
MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization...
November 2018: Nature Structural & Molecular Biology
Clement Nemoz, Virginie Ropars, Philippe Frit, Amandine Gontier, Pascal Drevet, Jinchao Yu, Raphaël Guerois, Aurelien Pitois, Audrey Comte, Christine Delteil, Nadia Barboule, Pierre Legrand, Sonia Baconnais, Yandong Yin, Satish Tadi, Emeline Barbet-Massin, Imre Berger, Eric Le Cam, Mauro Modesti, Eli Rothenberg, Patrick Calsou, Jean Baptiste Charbonnier
The Ku70-Ku80 (Ku) heterodimer binds rapidly and tightly to the ends of DNA double-strand breaks and recruits factors of the non-homologous end-joining (NHEJ) repair pathway through molecular interactions that remain unclear. We have determined crystal structures of the Ku-binding motifs (KBM) of the NHEJ proteins APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex. The two KBM motifs bind remote sites of the Ku80 α/β domain. The X-KBM occupies an internal pocket formed by an unprecedented large outward rotation of the Ku80 α/β domain...
October 2018: Nature Structural & Molecular Biology
Hayden R Schmidt, Robin M Betz, Ron O Dror, Andrew C Kruse
The σ1 receptor is a poorly understood membrane protein expressed throughout the human body. Ligands targeting the σ1 receptor are in clinical trials for treatment of Alzheimer's disease, ischemic stroke, and neuropathic pain. However, relatively little is known regarding the σ1 receptor's molecular function. Here, we present crystal structures of human σ1 receptor bound to the antagonists haloperidol and NE-100, and the agonist (+)-pentazocine, at crystallographic resolutions of 3.1 Å, 2.9 Å, and 3...
October 2018: Nature Structural & Molecular Biology
Zhen Sun, Dan Filipescu, Joshua Andrade, Alexandre Gaspar-Maia, Beatrix Ueberheide, Emily Bernstein
The histone variant macroH2A occupies large repressive domains throughout the genome; however, mechanisms underlying its precise deposition remain poorly understood. Here, we characterize de novo chromatin deposition of macroH2A2 using temporal genomic profiling in murine-derived fibroblasts devoid of all macroH2A isoforms. We find that macroH2A2 is first pervasively deposited genome wide at both steady-state domains and adjacent transcribed regions, the latter of which are subsequently pruned, establishing mature macroH2A2 domains...
October 2018: Nature Structural & Molecular Biology
Volker Kiessling, Alex J B Kreutzberger, Binyong Liang, Sarah B Nyenhuis, Patrick Seelheim, J David Castle, David S Cafiso, Lukas K Tamm
The regulated exocytotic release of neurotransmitter and hormones is accomplished by a complex protein machinery whose core consists of SNARE proteins and the calcium sensor synaptotagmin-1. We propose a mechanism in which the lipid membrane is intimately involved in coupling calcium sensing to release. We found that fusion of dense core vesicles, derived from rat PC12 cells, was strongly linked to the angle between the cytoplasmic domain of the SNARE complex and the plane of the target membrane. We propose that, as this tilt angle increases, force is exerted on the SNARE transmembrane domains to drive the merger of the two bilayers...
October 2018: Nature Structural & Molecular Biology
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