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Nature Structural & Molecular Biology

Martin S King, Paul G Crichton, Jonathan J Ruprecht, Edmund R S Kunji
In the version of this article originally published, references 6 and 7 were interchanged in the reference list. The error has been corrected in the HTML and PDF versions of the article.
September 14, 2018: Nature Structural & Molecular Biology
Nan Zhao, Vittorio Sebastiano, Natasha Moshkina, Nacho Mena, Judd Hultquist, David Jimenez-Morales, Yixuan Ma, Alex Rialdi, Randy Albrecht, Romain Fenouil, Maria Teresa Sánchez-Aparicio, Juan Ayllon, Sweta Ravisankar, Bahareh Haddad, Jessica Sook Yuin Ho, Diana Low, Jian Jin, Vyacheslav Yurchenko, Rab K Prinjha, Alexander Tarakhovsky, Massimo Squatrito, Dalila Pinto, Kimaada Allette, Minji Byun, Melissa Laird Smith, Robert Sebra, Ernesto Guccione, Terrence Tumpey, Nevan Krogan, Benjamin Greenbaum, Harm van Bakel, Adolfo García-Sastre, Ivan Marazzi
Viral infection perturbs host cells and can be used to uncover regulatory mechanisms controlling cellular responses and susceptibility to infections. Using cell biological, biochemical, and genetic tools, we reveal that influenza A virus (IAV) infection induces global transcriptional defects at the 3' ends of active host genes and RNA polymerase II (RNAPII) run-through into extragenic regions. Deregulated RNAPII leads to expression of aberrant RNAs (3' extensions and host-gene fusions) that ultimately cause global transcriptional downregulation of physiological transcripts, an effect influencing antiviral response and virulence...
September 3, 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
Vilius Kurauskas, Audrey Hessel, François Dehez, Christophe Chipot, Beate Bersch, Paul Schanda
No abstract text is available yet for this article.
September 3, 2018: Nature Structural & Molecular Biology
Hauke S Hillen, Dmitry Temiakov, Patrick Cramer
The mitochondrial genome is transcribed by a single-subunit DNA-dependent RNA polymerase (mtRNAP) and its auxiliary factors. Structural studies have elucidated how mtRNAP cooperates with its dedicated transcription factors to direct RNA synthesis: initiation factors TFAM and TFB2M assist in promoter-DNA binding and opening by mtRNAP while the elongation factor TEFM increases polymerase processivity to the levels required for synthesis of long polycistronic mtRNA transcripts. Here, we review the emerging body of structural and functional studies of human mitochondrial transcription, provide a molecular movie that can be used for teaching purposes and discuss the open questions to guide future directions of investigation...
September 2018: Nature Structural & Molecular Biology
Mingfeng Zhang, Dali Wang, Yunlu Kang, Jing-Xiang Wu, Fuqiang Yao, Chengfang Pan, Zhiqiang Yan, Chen Song, Lei Chen
Mechanosensitive ion channels convert mechanical stimuli into a flow of ions. These channels are widely distributed from bacteria to higher plants and humans, and are involved in many crucial physiological processes. Here we show that two members of the OSCA protein family in Arabidopsis thaliana, namely AtOSCA1.1 and AtOSCA3.1, belong to a new class of mechanosensitive ion channels. We solve the structure of the AtOSCA1.1 channel at 3.5-Å resolution and AtOSCA3.1 at 4.8-Å resolution by cryo-electron microscopy...
September 2018: Nature Structural & Molecular Biology
Miki Jishage, Xiaodi Yu, Yi Shi, Sai J Ganesan, Wei-Yi Chen, Andrej Sali, Brian T Chait, Francisco J Asturias, Robert G Roeder
Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal...
September 2018: Nature Structural & Molecular Biology
Kata Sarlós, Andreas S Biebricher, Anna H Bizard, Julia A M Bakx, Anna G Ferreté-Bonastre, Mauro Modesti, Manikandan Paramasivam, Qi Yao, Erwin J G Peterman, Gijs J L Wuite, Ian D Hickson
Faithful chromosome segregation requires that the sister chromatids be disjoined completely. Defective disjunction can lead to the persistence of histone-free threads of DNA known as ultra-fine bridges (UFBs) that connect the separating sister DNA molecules during anaphase. UFBs arise at specific genomic loci and can only be visualized by detection of associated proteins such as PICH, BLM, topoisomerase IIIα, and RPA. However, it remains unknown how these proteins work together to promote UFB processing. We used a combination of ensemble biochemistry and new single-molecule assays to reconstitute key steps of UFB recognition and processing by these human proteins in vitro...
September 2018: Nature Structural & Molecular Biology
Martin S King, Paul G Crichton, Jonathan J Ruprecht, Edmund R S Kunji
No abstract text is available yet for this article.
September 2018: Nature Structural & Molecular Biology
Kilian R Knoll, Sebastian Eustermann, Vanessa Niebauer, Elisa Oberbeckmann, Gabriele Stoehr, Kevin Schall, Alessandro Tosi, Marianne Schwarz, Andrea Buchfellner, Philipp Korber, Karl-Peter Hopfner
Nuclear actin (N-actin) and actin-related proteins (Arps) are critical components of several chromatin modulating complexes, including the chromatin remodeler INO80, but their function is largely elusive. Here, we report the crystal structure of the 180-kDa Arp8 module of Saccharomyces cerevisiae INO80 and establish its role in recognition of extranucleosomal linker DNA. Arp8 engages N-actin in a manner distinct from that of other actin-fold proteins and thereby specifies recruitment of the Arp4-N-actin heterodimer to a segmented scaffold of the helicase-SANT-associated (HSA) domain of Ino80...
September 2018: Nature Structural & Molecular Biology
Thomas G W Graham, Sean M Carney, Johannes C Walter, Joseph J Loparo
Nonhomologous end joining (NHEJ) is the primary pathway of DNA double-strand-break repair in vertebrate cells, yet how NHEJ factors assemble a synaptic complex that bridges DNA ends remains unclear. To address the role of XRCC4-like factor (XLF) in synaptic-complex assembly, we used single-molecule fluorescence imaging in Xenopus laevis egg extract, a system that efficiently joins DNA ends. We found that a single XLF dimer binds DNA substrates just before the formation of a ligation-competent synaptic complex between DNA ends...
September 2018: Nature Structural & Molecular Biology
Yi Zhang, Yongming Xue, Jiejun Shi, JaeWoo Ahn, Wenyi Mi, Muzaffar Ali, Xiaolu Wang, Brianna J Klein, Hong Wen, Wei Li, Xiaobing Shi, Tatiana G Kutateladze
Human p300 is a transcriptional co-activator and a major acetyltransferase that acetylates histones and other proteins facilitating gene transcription. The activity of p300 relies on the fine-tuned interactome that involves a dozen p300 domains and hundreds of binding partners and links p300 to a wide range of vital signaling events. Here, we report a novel function of the ZZ-type zinc finger (ZZ) of p300 as a reader of histone H3. We show that the ZZ domain and acetyllysine-recognizing bromodomain of p300 play critical roles in modulating p300 enzymatic activity and its association with chromatin...
September 2018: Nature Structural & Molecular Biology
Chris Miller
No abstract text is available yet for this article.
September 2018: Nature Structural & Molecular Biology
Maro Iliopoulou, Rory Nolan, Luis Alvarez, Yasunori Watanabe, Charles A Coomer, G Maria Jakobsdottir, Thomas A Bowden, Sergi Padilla-Parra
Little is known about the intermolecular dynamics and stoichiometry of the interactions of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) protein with its receptors and co-receptors on the host cell surface. Here we analyze time-resolved HIV-1 Env interactions with T-cell surface glycoprotein CD4 (CD4) and C-C chemokine receptor type 5 (CCR5) or C-X-C chemokine receptor type 4 (CXCR4) on the surface of cells, by combining multicolor super-resolution localization microscopy (direct stochastic optical reconstruction microscopy) with fluorescence fluctuation spectroscopy imaging...
September 2018: Nature Structural & Molecular Biology
Go Kasuya, Takanori Nakane, Takeshi Yokoyama, Yanyan Jia, Masato Inoue, Kengo Watanabe, Ryoki Nakamura, Tomohiro Nishizawa, Tsukasa Kusakizako, Akihisa Tsutsumi, Haruaki Yanagisawa, Naoshi Dohmae, Motoyuki Hattori, Hidenori Ichijo, Zhiqiang Yan, Masahide Kikkawa, Mikako Shirouzu, Ryuichiro Ishitani, Osamu Nureki
Maintenance of cell volume against osmotic change is crucial for proper cell functions. Leucine-rich repeat-containing 8 proteins are anion-selective channels that extrude anions to decrease the cell volume on cellular swelling. Here, we present the structure of human leucine-rich repeat-containing 8A, determined by single-particle cryo-electron microscopy. The structure shows a hexameric assembly, and the transmembrane region features a topology similar to gap junction channels. The LRR region, with 15 leucine-rich repeats, forms a long, twisted arc...
September 2018: Nature Structural & Molecular Biology
Appu K Singh, Luke L McGoldrick, Alexander I Sobolevsky
Transient receptor potential vanilloid subfamily member 3 (TRPV3) channel plays a crucial role in skin physiology and pathophysiology. Mutations in TRPV3 are associated with various skin diseases, including Olmsted syndrome, atopic dermatitis, and rosacea. Here we present the cryo-electron microscopy structures of full-length mouse TRPV3 in the closed apo and agonist-bound open states. The agonist binds three allosteric sites distal to the pore. Channel opening is accompanied by conformational changes in both the outer pore and the intracellular gate...
September 2018: Nature Structural & Molecular Biology
John D McCorvy, Daniel Wacker, Sheng Wang, Bemnat Agegnehu, Jing Liu, Katherine Lansu, Alexandra R Tribo, Reid H J Olsen, Tao Che, Jian Jin, Bryan L Roth
Serotonin (5-hydroxytryptamine; 5-HT) receptors modulate a variety of physiological processes ranging from perception, cognition and emotion to vascular and smooth muscle contraction, platelet aggregation, gastrointestinal function and reproduction. Drugs that interact with 5-HT receptors effectively treat diseases as diverse as migraine headaches, depression and obesity. Here we present four structures of a prototypical serotonin receptor-the human 5-HT2B receptor-in complex with chemically and pharmacologically diverse drugs, including methysergide, methylergonovine, lisuride and LY266097...
September 2018: Nature Structural & Molecular Biology
Natasha Jansz, Andrew Keniry, Marie Trussart, Heidi Bildsoe, Tamara Beck, Ian D Tonks, Arne W Mould, Peter Hickey, Kelsey Breslin, Megan Iminitoff, Matthew E Ritchie, Edwina McGlinn, Graham F Kay, James M Murphy, Marnie E Blewitt
The regulation of higher-order chromatin structure is complex and dynamic, and a full understanding of the suite of mechanisms governing this architecture is lacking. Here, we reveal the noncanonical SMC protein Smchd1 to be a novel regulator of long-range chromatin interactions in mice, and we add Smchd1 to the canon of epigenetic proteins required for Hox-gene regulation. The effect of losing Smchd1-dependent chromatin interactions has varying outcomes that depend on chromatin context. At autosomal targets transcriptionally sensitive to Smchd1 deletion, we found increased short-range interactions and ectopic enhancer activation...
September 2018: Nature Structural & Molecular Biology
Sandro Baldi, Stefan Krebs, Helmut Blum, Peter B Becker
The nature of chromatin as regular succession of nucleosomes has gained iconic status. However, since most nucleosomes in metazoans are poorly positioned it is unknown to which extent bulk genomic nucleosome repeat length reflects the regularity and spacing of nucleosome arrays at individual loci. We describe a new approach to map nucleosome array regularity and spacing through sequencing oligonucleosome-derived DNA by Illumina sequencing and emergent nanopore technology. In Drosophila cells, this revealed modulation of array regularity and nucleosome repeat length depending on functional chromatin states independently of nucleosome positioning and even in unmappable regions...
September 2018: Nature Structural & Molecular Biology
Marc Boehning, Claire Dugast-Darzacq, Marija Rankovic, Anders S Hansen, Taekyung Yu, Herve Marie-Nelly, David T McSwiggen, Goran Kokic, Gina M Dailey, Patrick Cramer, Xavier Darzacq, Markus Zweckstetter
The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is an intrinsically disordered low-complexity region that is critical for pre-mRNA transcription and processing. The CTD consists of hepta-amino acid repeats varying in number from 52 in humans to 26 in yeast. Here we report that human and yeast CTDs undergo cooperative liquid phase separation, with the shorter yeast CTD forming less-stable droplets. In human cells, truncation of the CTD to the length of the yeast CTD decreases Pol II clustering and chromatin association, whereas CTD extension has the opposite effect...
September 2018: Nature Structural & Molecular Biology
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