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Nature Structural & Molecular Biology

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https://www.readbyqxmd.com/read/28530707/a-mili-independent-pirna-biogenesis-pathway-empowers-partial-germline-reprogramming
#1
Lina Vasiliauskaitė, Dimitrios Vitsios, Rebecca V Berrens, Claudia Carrieri, Wolf Reik, Anton J Enright, Dónal O'Carroll
In mice, the pathway involving PIWI and PIWI-interacting RNA (PIWI-piRNA) is essential to re-establish transposon silencing during male-germline reprogramming. The cytoplasmic PIWI protein MILI mediates piRNA-guided transposon RNA cleavage as well as piRNA amplification. MIWI2's binding to piRNA and its nuclear localization are proposed to be dependent upon MILI function. Here, we demonstrate the existence of a piRNA biogenesis pathway that sustains partial MIWI2 function and reprogramming activity in the absence of MILI...
May 22, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28504696/5-formylcytosine-does-not-change-the-global-structure-of-dna
#2
Jack S Hardwick, Denis Ptchelkine, Afaf H El-Sagheer, Ian Tear, Daniel Singleton, Simon E V Phillips, Andrew N Lane, Tom Brown
The mechanism by which the recently identified DNA modification 5-formylcytosine ((f)C) is recognized by epigenetic writer and reader proteins is not known. Recently, an unusual DNA structure, F-DNA, has been proposed as the basis for enzyme recognition of clusters of (f)C. We used NMR and X-ray crystallography to compare several modified DNA duplexes with unmodified analogs and found that in the crystal state the duplexes all belong to the A family, whereas in solution they are all members of the B family...
May 15, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28481356/the-myosin-mesa-and-the-basis-of-hypercontractility-caused-by-hypertrophic-cardiomyopathy-mutations
#3
Suman Nag, Darshan V Trivedi, Saswata S Sarkar, Arjun S Adhikari, Margaret S Sunitha, Shirley Sutton, Kathleen M Ruppel, James A Spudich
Hypertrophic cardiomyopathy (HCM) is primarily caused by mutations in β-cardiac myosin and myosin-binding protein-C (MyBP-C). Changes in the contractile parameters of myosin measured so far do not explain the clinical hypercontractility caused by such mutations. We propose that hypercontractility is due to an increase in the number of myosin heads (S1) that are accessible for force production. In support of this hypothesis, we demonstrate myosin tail (S2)-dependent functional regulation of actin-activated human β-cardiac myosin ATPase...
May 8, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28459447/human-ctp-synthase-filament-structure-reveals-the-active-enzyme-conformation
#4
Eric M Lynch, Derrick R Hicks, Matthew Shepherd, James A Endrizzi, Allison Maker, Jesse M Hansen, Rachael M Barry, Zemer Gitai, Enoch P Baldwin, Justin M Kollman
The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria, polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we show that for human CTPS, polymerization increases catalytic activity. The cryo-EM structures of bacterial and human CTPS filaments differ considerably in overall architecture and in the conformation of the CTPS protomer, explaining the divergent consequences of polymerization on activity. The structure of human CTPS filament, the first structure of the full-length human enzyme, reveals a novel active conformation...
May 1, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28436945/adar1-controls-apoptosis-of-stressed-cells-by-inhibiting-staufen1-mediated-mrna-decay
#5
Masayuki Sakurai, Yusuke Shiromoto, Hiromitsu Ota, Chunzi Song, Andrew V Kossenkov, Jayamanna Wickramasinghe, Louise C Showe, Emmanuel Skordalakes, Hsin-Yao Tang, David W Speicher, Kazuko Nishikura
Both p150 and p110 isoforms of ADAR1 convert adenosine to inosine in double-stranded RNA (dsRNA). ADAR1p150 suppresses the dsRNA-sensing mechanism that activates MDA5-MAVS-IFN signaling in the cytoplasm. In contrast, the biological function of the ADAR1p110 isoform, which is usually located in the nucleus, is largely unknown. Here, we show that stress-activated phosphorylation of ADAR1p110 by MKK6-p38-MSK MAP kinases promotes its binding to Exportin-5 and its export from the nucleus. After translocating to the cytoplasm, ADAR1p110 suppresses apoptosis in stressed cells by protecting many antiapoptotic gene transcripts that contain 3'-untranslated-region dsRNA structures primarily comprising inverted Alu repeats...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28436944/active-and-poised-promoter-states-drive-folding-of-the-extended-hoxb-locus-in-mouse-embryonic-stem-cells
#6
Mariano Barbieri, Sheila Q Xie, Elena Torlai Triglia, Andrea M Chiariello, Simona Bianco, Inês de Santiago, Miguel R Branco, David Rueda, Mario Nicodemi, Ana Pombo
Gene expression states influence the 3D conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features that define promoter activation states or binding sites for the transcription factor CTCF...
April 24, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28471430/dna-rna-hybrids-the-risks-of-dna-breakage-during-transcription
#7
Andrés Aguilera, Belén Gómez-González
Although R loops can occur at different genomic locations, the factors that determine their formation and frequency remain unclear. Emerging evidence indicates that DNA breaks stimulate DNA-RNA hybrid formation. Here, we discuss the possibility that formation of hybrids may be an inevitable risk of DNA breaks that occur within actively transcribed regions. While such hybrids must be removed to permit repair, their potential role as repair intermediates remains to be established.
May 4, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28471429/capturing-heterogeneity-single-cell-structures-of-the-3d-genome
#8
Elzo de Wit
No abstract text is available yet for this article.
May 4, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28471428/splicing-of-ezh1-gets-muscle-out-of-stressful-situations
#9
Marjorie Brand, F Jeffrey Dilworth
No abstract text is available yet for this article.
May 4, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28471427/carb-cutting-works-better-with-a-partner
#10
Jennifer J Kohler
No abstract text is available yet for this article.
May 4, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28471426/anna-tramontano-1957-2017
#11
Janet M Thornton, Alfonso Valencia, Torsten Schwede
No abstract text is available yet for this article.
May 4, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28414322/parkin-phosphoubiquitin-complex-reveals-cryptic-ubiquitin-binding-site-required-for-rbr-ligase-activity
#12
Atul Kumar, Viduth K Chaugule, Tara E C Condos, Kathryn R Barber, Clare Johnson, Rachel Toth, Ramasubramanian Sundaramoorthy, Axel Knebel, Gary S Shaw, Helen Walden
RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a catalytic RBR module but are usually autoinhibited and activated via distinct mechanisms. Recent insights into Parkin regulation predict large, unknown conformational changes during Parkin activation. However, current data on active RBR ligases reflect the absence of regulatory domains...
May 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28414321/an-orthogonal-single-molecule-experiment-reveals-multiple-attempt-dynamics-of-type-ia-topoisomerases
#13
Kathryn H Gunn, John F Marko, Alfonso Mondragón
Topoisomerases are enzymes that are involved in maintaining the topological state of cellular DNA. Their dynamic characteristics remain poorly understood despite numerous structural, biophysical and biochemical studies. Recent single-molecule experiments revealed that an important feature of the type IA topoisomerase mechanism is the presence of pauses between relaxation events. However, these experiments could not determine whether the protein remains DNA bound during the pauses or what relationship may exist between protein domain movements and topological changes in the DNA...
May 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28394326/intraflagellar-transport-dynein-is-autoinhibited-by-trapping-of-its-mechanical-and-track-binding-elements
#14
Katerina Toropova, Miroslav Mladenov, Anthony J Roberts
Cilia are multifunctional organelles that are constructed using intraflagellar transport (IFT) of cargo to and from their tip. It is widely held that the retrograde IFT motor, dynein-2, must be controlled in order to reach the ciliary tip and then unleashed to power the return journey. However, the mechanism is unknown. Here, we systematically define the mechanochemistry of human dynein-2 motors as monomers, dimers, and multimotor assemblies with kinesin-II. Combining these data with insights from single-particle EM, we discover that dynein-2 dimers are intrinsically autoinhibited...
May 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28394325/structural-basis-for-lipopolysaccharide-extraction-by-abc-transporter-lptb2fg
#15
Qingshan Luo, Xu Yang, Shan Yu, Huigang Shi, Kun Wang, Le Xiao, Guangyu Zhu, Chuanqi Sun, Tingting Li, Dianfan Li, Xinzheng Zhang, Min Zhou, Yihua Huang
After biosynthesis, bacterial lipopolysaccharides (LPS) are transiently anchored to the outer leaflet of the inner membrane (IM). The ATP-binding cassette (ABC) transporter LptB2FG extracts LPS molecules from the IM and transports them to the outer membrane. Here we report the crystal structure of nucleotide-free LptB2FG from Pseudomonas aeruginosa. The structure reveals that lipopolysaccharide transport proteins LptF and LptG each contain a transmembrane domain (TMD), a periplasmic β-jellyroll-like domain and a coupling helix that interacts with LptB on the cytoplasmic side...
May 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28368393/structure-of-the-40s-abce1-post-splitting-complex-in-ribosome-recycling-and-translation-initiation
#16
André Heuer, Milan Gerovac, Christian Schmidt, Simon Trowitzsch, Anne Preis, Peter Kötter, Otto Berninghausen, Thomas Becker, Roland Beckmann, Robert Tampé
The essential ATP-binding cassette protein ABCE1 splits 80S ribosomes into 60S and 40S subunits after canonical termination or quality-control-based mRNA surveillance processes. However, the underlying splitting mechanism remains enigmatic. Here, we present a cryo-EM structure of the yeast 40S-ABCE1 post-splitting complex at 3.9-Å resolution. Compared to the pre-splitting state, we observe repositioning of ABCE1's iron-sulfur cluster domain, which rotates 150° into a binding pocket on the 40S subunit. This repositioning explains a newly observed anti-association activity of ABCE1...
May 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28346433/a-cytosolic-ezh1-isoform-modulates-a-prc2-ezh1-epigenetic-adaptive-response-in-postmitotic-cells
#17
Beatrice Bodega, Federica Marasca, Valeria Ranzani, Alessandro Cherubini, Francesco Della Valle, Maria Victoria Neguembor, Michel Wassef, Alessio Zippo, Chiara Lanzuolo, Massimiliano Pagani, Valerio Orlando
The evolution of chromatin-based epigenetic cell memory may be driven not only by the necessity for cells to stably maintain transcription programs, but also by the need to recognize signals and allow plastic responses to environmental stimuli. The mechanistic role of the epigenome in adult postmitotic tissues, however, remains largely unknown. In vertebrates, two variants of the Polycomb repressive complex (PRC2-Ezh2 and PRC2-Ezh1) control gene silencing via methylation of histone H3 on Lys27 (H3K27me). Here we describe a reversible mechanism that involves a novel isoform of Ezh1 (Ezh1β)...
May 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28384136/remodelers-tap-into-nucleosome-plasticity
#18
Hari R Singh, Magdalena Murawska, Andreas G Ladurner
No abstract text is available yet for this article.
April 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28384135/separase-securin-complex-a-cunning-way-to-control-chromosome-segregation
#19
Martin R Singleton, Frank Uhlmann
No abstract text is available yet for this article.
April 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28384134/surveillance-states
#20
Pradyot Dash, Paul G Thomas
No abstract text is available yet for this article.
April 6, 2017: Nature Structural & Molecular Biology
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