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https://www.readbyqxmd.com/read/28729462/archives-of-and-for-science-archives-for-molecular-biology-preserve-the-heritage-of-science-beyond-the-published-record-for-future%C3%A2-scholars
#1
Anne-Flore Laloë
No abstract text is available yet for this article.
July 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28729461/morphology-of-the-archaellar-motor-and-associated-cytoplasmic-cone-in-thermococcus-kodakaraensis
#2
Ariane Briegel, Catherine M Oikonomou, Yi-Wei Chang, Andreas Kjær, Audrey N Huang, Ki Woo Kim, Debnath Ghosal, Hong H Nguyen, Dorothy Kenny, Rachel R Ogorzalek Loo, Robert P Gunsalus, Grant J Jensen
Archaeal swimming motility is driven by archaella: rotary motors attached to long extracellular filaments. The structure of these motors, and particularly how they are anchored in the absence of a peptidoglycan cell wall, is unknown. Here, we use electron cryotomography to visualize the archaellar basal body in vivo in Thermococcus kodakaraensis KOD1. Compared to the homologous bacterial type IV pilus (T4P), we observe structural similarities as well as several unique features. While the position of the cytoplasmic ATPase appears conserved, it is not braced by linkages that extend upward through the cell envelope as in the T4P, but rather by cytoplasmic components that attach it to a large conical frustum up to 500 nm in diameter at its base...
July 19, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28720649/the-greatest-kinetochore-show-on-earth
#3
Gerben Vader, Andrea Musacchio
Coordinated chromosome duplication and segregation is key to the existence of every organism on our planet. In eukaryotes, sophisticated protein assemblies called kinetochores are universally required for chromosome segregation, but their protein composition can diverge across the eukaryotic tree of life. In this issue of EMBO Reports, van Hooff et al [1] shed light on kinetochore evolution with a comprehensive study of kinetochore composition across 90 phylogenetically diverse eukaryotes. They show that certain kinetochore complexes have taken distinct evolutionary paths to arrive at a strikingly broad compositional array in present-day eukaryotes, providing exciting new insights into the origins, function, and flexibility of eukaryotic kinetochores...
July 18, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28710093/the-ciliary-membrane-associated-proteome-reveals-actin-binding-proteins-as-key-components-of-cilia
#4
Priyanka Kohli, Martin Höhne, Christian Jüngst, Sabine Bertsch, Lena K Ebert, Astrid C Schauss, Thomas Benzing, Markus M Rinschen, Bernhard Schermer
Primary cilia are sensory, antennae-like organelles present on the surface of many cell types. They have been involved in a variety of diseases collectively termed ciliopathies. As cilia are essential regulators of cell signaling, the composition of the ciliary membrane needs to be strictly regulated. To understand regulatory processes at the ciliary membrane, we report the targeting of a genetically engineered enzyme specifically to the ciliary membrane to allow biotinylation and identification of the membrane-associated proteome...
July 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28705801/the-mir-15-family-reinforces-the-transition-from-proliferation-to-differentiation-in-pre-b-cells
#5
Silke E Lindner, Michael Lohmüller, Bianka Kotkamp, Fabian Schuler, Zeynep Knust, Andreas Villunger, Sebastian Herzog
Precursor B lymphocytes expand upon expression of a pre-B cell receptor (pre-BCR), but then transit into a resting state in which immunoglobulin light chain gene recombination is initiated. This bi-phasic sequence is orchestrated by the IL-7 receptor (IL-7R) and pre-BCR signaling, respectively, but little is known about microRNAs fine-tuning these events. Here, we show that pre-B cells lacking miR-15 family functions exhibit prolonged proliferation due to aberrant expression of the target genes cyclin E1 and D3...
July 13, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28701327/tetanus-neurotoxin-conformational-plasticity-as-an-adaptive-strategy
#6
Mauricio Montal
No abstract text is available yet for this article.
July 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28701326/a%C3%AE-seeding-potency-peaks-in-the-early-stages-of-cerebral-%C3%AE-amyloidosis
#7
Lan Ye, Jay Rasmussen, Stephan A Kaeser, Anne-Marie Marzesco, Ulrike Obermüller, Jasmin Mahler, Juliane Schelle, Jörg Odenthal, Christian Krüger, Sarah K Fritschi, Lary C Walker, Matthias Staufenbiel, Frank Baumann, Mathias Jucker
Little is known about the extent to which pathogenic factors drive the development of Alzheimer's disease (AD) at different stages of the long preclinical and clinical phases. Given that the aggregation of the β-amyloid peptide (Aβ) is an important factor in AD pathogenesis, we asked whether Aβ seeds from brain extracts of mice at different stages of amyloid deposition differ in their biological activity. Specifically, we assessed the effect of age on Aβ seeding activity in two mouse models of cerebral Aβ amyloidosis (APPPS1 and APP23) with different ages of onset and rates of progression of Aβ deposition...
July 12, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28684399/loss-of-the-canonical-spindle-orientation-function-in-the-pins-lgn-homolog-ags3
#8
Mehdi Saadaoui, Daijiro Konno, Karine Loulier, Rosette Goiame, Vaibhav Jadhav, Marina Mapelli, Fumio Matsuzaki, Xavier Morin
In many cell types, mitotic spindle orientation relies on the canonical "LGN complex" composed of Pins/LGN, Mud/NuMA, and Gαi subunits. Membrane localization of this complex recruits motor force generators that pull on astral microtubules to orient the spindle. Drosophila Pins shares highly conserved functional domains with its two vertebrate homologs LGN and AGS3. Whereas the role of Pins and LGN in oriented divisions is extensively documented, involvement of AGS3 remains controversial. Here, we show that AGS3 is not required for planar divisions of neural progenitors in the mouse neocortex...
July 6, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28676478/gwas-and-cognitive-abilities-why-correlations-are-inevitable-and%C3%A2-meaningless-gwa-studies-to-identify-genetic-factors-for-educational-achievements-largely-ignore-underlying-social-structures-and-dynamics
#9
https://www.readbyqxmd.com/read/28655748/structural-and-functional-analysis-of-the-gabarap-interaction-motif-gim
#10
Vladimir V Rogov, Alexandra Stolz, Arvind C Ravicahandran, Diana O Rios-Szwed, Hironori Suzuki, Andreas Kniss, Frank Löhr, Soichi Wakatsuki, Volker Dötsch, Ivan Dikic, Renwick Cj Dobson, David G McEwan
Through the canonical LC3 interaction motif (LIR), [W/F/Y]-X1-X2-[I/L/V], protein complexes are recruited to autophagosomes to perform their functions as either autophagy adaptors or receptors. How these adaptors/receptors selectively interact with either LC3 or GABARAP families remains unclear. Herein, we determine the range of selectivity of 30 known core LIR motifs towards individual LC3s and GABARAPs. From these, we define a G ABARAP I nteraction M otif (GIM) sequence ([W/F]-[V/I]-X2-V) that the adaptor protein PLEKHM1 tightly conforms to...
June 27, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28652379/the-mutant-p53-id4-complex-controls-vegfa-isoforms-by-recruiting-lncrna-malat1
#11
Magdalena Pruszko, Elisa Milano, Mattia Forcato, Sara Donzelli, Federica Ganci, Silvia Di Agostino, Simone De Panfilis, Francesco Fazi, David O Bates, Silvio Bicciato, Maciej Zylicz, Alicja Zylicz, Giovanni Blandino, Giulia Fontemaggi
The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear speckles, where it interacts with a subset of splicing factors and modulates their activity. In this study, we demonstrate that oncogenic splicing factor SRSF1 bridges MALAT1 to mutant p53 and ID4 proteins in breast cancer cells. Mutant p53 and ID4 delocalize MALAT1 from nuclear speckles and favor its association with chromatin...
June 26, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28645943/the-structure-of-the-tetanus-toxin-reveals-ph-mediated-domain-dynamics
#12
Geoffrey Masuyer, Julian Conrad, Pål Stenmark
The tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a "closed" domain arrangement stabilised by two disulphide bridges, and the molecular details of the toxin's interaction with its polysaccharide receptor...
June 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28642229/evolutionary-dynamics-of-the-kinetochore-network-in-eukaryotes-as-revealed-by-comparative-genomics
#13
Jolien Je van Hooff, Eelco Tromer, Leny M van Wijk, Berend Snel, Geert Jpl Kops
During eukaryotic cell division, the sister chromatids of duplicated chromosomes are pulled apart by microtubules, which connect via kinetochores. The kinetochore is a multiprotein structure that links centromeres to microtubules, and that emits molecular signals in order to safeguard the equal distribution of duplicated chromosomes over daughter cells. Although microtubule-mediated chromosome segregation is evolutionary conserved, kinetochore compositions seem to have diverged. To systematically inventory kinetochore diversity and to reconstruct its evolution, we determined orthologs of 70 kinetochore proteins in 90 phylogenetically diverse eukaryotes...
June 22, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28637682/cellular-mechanism-of-fibril-formation-from-serum-amyloid-a1-protein
#14
Stephanie Claus, Katrin Meinhardt, Tobias Aumüller, Ioana Puscalau-Girtu, Julia Linder, Christian Haupt, Paul Walther, Tatiana Syrovets, Thomas Simmet, Marcus Fändrich
Serum amyloid A1 (SAA1) is an apolipoprotein that binds to the high-density lipoprotein (HDL) fraction of the serum and constitutes the fibril precursor protein in systemic AA amyloidosis. We here show that HDL binding blocks fibril formation from soluble SAA1 protein, whereas internalization into mononuclear phagocytes leads to the formation of amyloid. SAA1 aggregation in the cell model disturbs the integrity of vesicular membranes and leads to lysosomal leakage and apoptotic death. The formed amyloid becomes deposited outside the cell where it can seed the fibrillation of extracellular SAA1...
June 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28623188/gli1-induced-deubiquitinase-usp48-aids-glioblastoma-tumorigenesis-by-stabilizing-gli1
#15
Aidong Zhou, Kangyu Lin, Sicong Zhang, Li Ma, Jianfei Xue, Saint-Aaron Morris, Kenneth D Aldape, Suyun Huang
Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein. Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly. In glioblastoma cells, knockdown of USP48 inhibits cell proliferation and the expression of Gli1's downstream targets, which leads to repressed glioblastoma tumorigenesis...
June 16, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28623187/control-of-box-c-d-snornp-assembly-by-n-6-methylation-of-adenine
#16
Lin Huang, Saira Ashraf, Jia Wang, David Mj Lilley
N(6)-methyladenine is the most widespread mRNA modification. A subset of human box C/D snoRNA species have target GAC sequences that lead to formation of N(6)-methyladenine at a key trans Hoogsteen-sugar A·G base pair, of which half are methylated in vivo The GAC target is conserved only in those that are methylated. Methylation prevents binding of the 15.5-kDa protein and the induced folding of the RNA Thus, the assembly of the box C/D snoRNP could in principle be regulated by RNA methylation at its critical first stage...
June 16, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615293/looping-out-mechanism-for-resolution-of-replicative-stress-at-telomeres
#17
Tianpeng Zhang, Zepeng Zhang, Feng Li, Qian Hu, Haiying Liu, Mengfan Tang, Wenbin Ma, Junjiu Huang, Zhou Songyang, Yikang Rong, Shichuan Zhang, Benjamin Pc Chen, Yong Zhao
Repetitive DNA is prone to replication fork stalling, which can lead to genome instability. Here, we find that replication fork stalling at telomeres leads to the formation of t-circle-tails, a new extrachromosomal structure that consists of circular telomeric DNA with a single-stranded tail. Structurally, the t-circle-tail resembles cyclized leading or lagging replication intermediates that are excised from the genome by topoisomerase II-mediated cleavage. We also show that the DNA damage repair machinery NHEJ is required for the formation of t-circle-tails and for the resolution of stalled replication forks, suggesting that NHEJ, which is normally constitutively suppressed at telomeres, is activated in the context of replication stress...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615292/rtt101-mms1-mms22-coordinates-replication-coupled-sister-chromatid-cohesion-and-nucleosome-assembly
#18
Jingjing Zhang, Di Shi, Xiaoli Li, Lin Ding, Jun Tang, Cong Liu, Katsuhiko Shirahige, Qinhong Cao, Huiqiang Lou
Two sister chromatids must be held together by a cohesion process from their synthesis during S phase to segregation in anaphase. Despite its pivotal role in accurate chromosome segregation, how cohesion is established remains elusive. Here, we demonstrate that yeast Rtt101-Mms1, Cul4 family E3 ubiquitin ligases are stronger dosage suppressors of loss-of-function eco1 mutants than PCNA The essential cohesion reaction, Eco1-catalyzed Smc3 acetylation is reduced in the absence of Rtt101-Mms1. One of the adaptor subunits, Mms22, associates directly with Eco1...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615291/high-affinity-cooperative-ca-2-binding-by-micu1-micu2-serves-as-an-on-off-switch-for-the%C3%A2-uniporter
#19
Kimberli J Kamer, Zenon Grabarek, Vamsi K Mootha
The mitochondrial calcium uniporter is a Ca(2+)-activated Ca(2+) channel that is essential for dynamic modulation of mitochondrial function in response to cellular Ca(2+) signals. It is regulated by two paralogous EF-hand proteins-MICU1 and MICU2, but the mechanism is unknown. Here, we demonstrate that both MICU1 and MICU2 are stabilized by Ca(2+) We reconstitute the MICU1-MICU2 heterodimer and demonstrate that it binds Ca(2+) cooperatively with high affinity. We discover that both MICU1 and MICU2 exhibit affinity for the mitochondria-specific lipid cardiolipin...
June 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28615290/a-post-translational-modification-switch-controls-coactivator-function-of-histone-methyltransferases-g9a-and-glp
#20
Coralie Poulard, Danielle Bittencourt, Dai-Ying Wu, Yixin Hu, Daniel S Gerke, Michael R Stallcup
Like many transcription regulators, histone methyltransferases G9a and G9a-like protein (GLP) can act gene-specifically as coregulators, but mechanisms controlling this specificity are mostly unknown. We show that adjacent post-translational methylation and phosphorylation regulate binding of G9a and GLP to heterochromatin protein 1 gamma (HP1γ), formation of a ternary complex with the glucocorticoid receptor (GR) on chromatin, and function of G9a and GLP as coactivators for a subset of GR target genes. HP1γ is recruited by G9a and GLP to GR binding sites associated with genes that require G9a, GLP, and HP1γ for glucocorticoid-stimulated transcription...
June 14, 2017: EMBO Reports
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