journal
MENU ▼
Read by QxMD icon Read
search

Nature Structural & Molecular Biology

journal
https://www.readbyqxmd.com/read/28067918/structural-insights-into-the-secretin-translocation-channel-in-the-type-ii-secretion-system
#1
Zhaofeng Yan, Meng Yin, Dandan Xu, Yongqun Zhu, Xueming Li
The secretin GspD of the type II secretion system (T2SS) forms a channel across the outer membrane in Gram-negative bacteria to transport substrates from the periplasm to the extracellular milieu. The lack of an atomic-resolution structure of the GspD channel hinders the investigation of substrate translocation mechanism of T2SS. Here we report cryo-EM structures of two GspD channels (∼1 MDa), from Escherichia coli K12 and Vibrio cholerae, at ∼3 Å resolution. The structures reveal a pentadecameric channel architecture, wherein three rings of GspD N domains form the periplasmic channel...
January 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28067917/structural-insights-into-a-unique-hsp70-hsp40-interaction-in-the-eukaryotic-ribosome-associated-complex
#2
Felix Alexander Weyer, Andrea Gumiero, Genís Valentín Gesé, Karine Lapouge, Irmgard Sinning
Cotranslational chaperones assist de novo folding of nascent polypeptides, prevent them from aggregating and modulate translation. The ribosome-associated complex (RAC) is unique in that the Hsp40 protein Zuo1 and the atypical Hsp70 chaperone Ssz1 form a stable heterodimer, which acts as a cochaperone for the Hsp70 chaperone Ssb. Here we present the structure of the Chaetomium thermophilum RAC core comprising Ssz1 and the Zuo1 N terminus. We show how the conserved allostery of Hsp70 proteins is abolished and this Hsp70-Hsp40 pair is molded into a functional unit...
January 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28067916/self-correcting-mismatches-during-high-fidelity-dna-replication
#3
Rafael Fernandez-Leiro, Julian Conrad, Ji-Chun Yang, Stefan M V Freund, Sjors H W Scheres, Meindert H Lamers
Faithful DNA replication is essential to all forms of life and depends on the action of 3'-5' exonucleases that remove misincorporated nucleotides from the newly synthesized strand. However, how the DNA is transferred from the polymerase to the exonuclease active site is not known. Here we present the cryo-EM structure of the editing mode of the catalytic core of the Escherichia coli replisome, revealing a dramatic distortion of the DNA whereby the polymerase thumb domain acts as a wedge that separates the two DNA strands...
January 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28067915/histone-degradation-in-response-to-dna-damage-enhances-chromatin-dynamics-and-recombination-rates
#4
Michael H Hauer, Andrew Seeber, Vijender Singh, Raphael Thierry, Ragna Sack, Assaf Amitai, Mariya Kryzhanovska, Jan Eglinger, David Holcman, Tom Owen-Hughes, Susan M Gasser
Nucleosomes are essential for proper chromatin organization and the maintenance of genome integrity. Histones are post-translationally modified and often evicted at sites of DNA breaks, facilitating the recruitment of repair factors. Whether such chromatin changes are localized or genome-wide is debated. Here we show that cellular levels of histones drop 20-40% in response to DNA damage. This histone loss occurs from chromatin, is proteasome-mediated and requires both the DNA damage checkpoint and the INO80 nucleosome remodeler...
January 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28067914/structure-of-the-immature-zika-virus-at-9-%C3%A3-resolution
#5
Vidya Mangala Prasad, Andrew S Miller, Thomas Klose, Devika Sirohi, Geeta Buda, Wen Jiang, Richard J Kuhn, Michael G Rossmann
The current Zika virus (ZIKV) epidemic is characterized by severe pathogenicity in both children and adults. Sequence changes in ZIKV since its first isolation are apparent when pre-epidemic strains are compared with those causing the current epidemic. However, the residues that are responsible for ZIKV pathogenicity are largely unknown. Here we report the cryo-electron microscopy (cryo-EM) structure of the immature ZIKV at 9-Å resolution. The cryo-EM map was fitted with the crystal structures of the precursor membrane and envelope glycoproteins and was shown to be similar to the structures of other known immature flaviviruses...
January 9, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28024149/crystal-structure-of-the-mop-flippase-murj-in-an-inward-facing-conformation
#6
Alvin C Y Kuk, Ellene H Mashalidis, Seok-Yong Lee
Peptidoglycan (PG) protects bacteria from osmotic lysis, and its biogenesis is a key antibiotic target. A central step in PG biosynthesis is flipping of the lipid-linked PG precursor lipid II across the cytoplasmic membrane for subsequent incorporation into PG. MurJ, part of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) transporter superfamily, was recently shown to carry out this process. However, understanding of how MurJ flips lipid II, and of how MOP transporters operate in general, remains limited due to a lack of structural information...
December 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28024148/solution-structure-of-discoidal-high-density-lipoprotein-particles-with-a-shortened-apolipoprotein-a-i
#7
Stefan Bibow, Yevhen Polyhach, Cédric Eichmann, Celestine N Chi, Julia Kowal, Stefan Albiez, Robert A McLeod, Henning Stahlberg, Gunnar Jeschke, Peter Güntert, Roland Riek
High-density lipoprotein (HDL) particles are cholesterol and lipid transport containers. Mature HDL particles destined for the liver develop through the formation of intermediate discoidal HDL particles, which are the primary acceptors for cholesterol. Here we present the three-dimensional structure of reconstituted discoidal HDL (rdHDL) particles, using a shortened construct of human apolipoprotein A-I, determined from a combination of nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and transmission electron microscopy (TEM) data...
December 26, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27991905/structure-of-the-polycystic-kidney-disease-trp-channel-polycystin-2-pc2
#8
Mariana Grieben, Ashley C W Pike, Chitra A Shintre, Elisa Venturi, Sam El-Ajouz, Annamaria Tessitore, Leela Shrestha, Shubhashish Mukhopadhyay, Pravin Mahajan, Rod Chalk, Nicola A Burgess-Brown, Rebecca Sitsapesan, Juha T Huiskonen, Elisabeth P Carpenter
Mutations in either polycystin-1 (PC1 or PKD1) or polycystin-2 (PC2, PKD2 or TRPP1) cause autosomal-dominant polycystic kidney disease (ADPKD) through unknown mechanisms. Here we present the structure of human PC2 in a closed conformation, solved by electron cryomicroscopy at 4.2-Å resolution. The structure reveals a novel polycystin-specific 'tetragonal opening for polycystins' (TOP) domain tightly bound to the top of a classic transient receptor potential (TRP) channel structure. The TOP domain is formed from two extensions to the voltage-sensor-like domain (VSLD); it covers the channel's endoplasmic reticulum lumen or extracellular surface and encloses an upper vestibule, above the pore filter, without blocking the ion-conduction pathway...
December 19, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27991904/pif1-family-helicases-cooperatively-suppress-widespread-replication-fork-arrest-at-trna-genes
#9
Joseph S Osmundson, Jayashree Kumar, Rani Yeung, Duncan J Smith
Saccharomyces cerevisiae expresses two Pif1-family helicases-Pif1 and Rrm3-which have been reported to play distinct roles in numerous nuclear processes. Here, we systematically characterized the roles of Pif1 helicases in replisome progression and lagging-strand synthesis in S. cerevisiae. We demonstrate that either Pif1 or Rrm3 redundantly stimulates strand displacement by DNA polymerase δ during lagging-strand synthesis. By analyzing replisome mobility in pif1 and rrm3 mutants, we show that Rrm3, with a partially redundant contribution from Pif1, suppresses widespread terminal arrest of the replisome at tRNA genes...
December 19, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27991903/structural-basis-for-targeted-dna-cytosine-deamination-and-mutagenesis-by-apobec3a-and-apobec3b
#10
Ke Shi, Michael A Carpenter, Surajit Banerjee, Nadine M Shaban, Kayo Kurahashi, Daniel J Salamango, Jennifer L McCann, Gabriel J Starrett, Justin V Duffy, Özlem Demir, Rommie E Amaro, Daniel A Harki, Reuben S Harris, Hideki Aihara
APOBEC-catalyzed cytosine-to-uracil deamination of single-stranded DNA (ssDNA) has beneficial functions in immunity and detrimental effects in cancer. APOBEC enzymes have intrinsic dinucleotide specificities that impart hallmark mutation signatures. Although numerous structures have been solved, mechanisms for global ssDNA recognition and local target-sequence selection remain unclear. Here we report crystal structures of human APOBEC3A and a chimera of human APOBEC3B and APOBEC3A bound to ssDNA at 3.1-Å and 1...
December 19, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27991902/crystal-structures-of-human-glycine-receptor-%C3%AE-3-bound-to-a-novel-class-of-analgesic-potentiators
#11
Xin Huang, Paul L Shaffer, Shawn Ayube, Howard Bregman, Hao Chen, Sonya G Lehto, Jason A Luther, David J Matson, Stefan I McDonough, Klaus Michelsen, Matthew H Plant, Stephen Schneider, Jeffrey R Simard, Yohannes Teffera, Shuyan Yi, Maosheng Zhang, Erin F DiMauro, Jacinthe Gingras
Current therapies to treat persistent pain and neuropathic pain are limited by poor efficacy, side effects and risk of addiction. Here, we present a novel class of potent selective, central nervous system (CNS)-penetrant potentiators of glycine receptors (GlyRs), ligand-gated ion channels expressed in the CNS. AM-1488 increased the response to exogenous glycine in mouse spinal cord and significantly reversed mechanical allodynia induced by nerve injury in a mouse model of neuropathic pain. We obtained an X-ray crystal structure of human homopentameric GlyRα3 in complex with AM-3607, a potentiator of the same class with increased potency, and the agonist glycine, at 2...
December 19, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27941862/cryo-em-structures-of-human-rad51-recombinase-filaments-during-catalysis-of-dna-strand-exchange
#12
Jingfei Xu, Lingyun Zhao, Yuanyuan Xu, Weixing Zhao, Patrick Sung, Hong-Wei Wang
The central step in eukaryotic homologous recombination (HR) is ATP-dependent DNA-strand exchange mediated by the Rad51 recombinase. In this process, Rad51 assembles on single-stranded DNA (ssDNA) and generates a helical filament that is able to search for and invade homologous double-stranded DNA (dsDNA), thus leading to strand separation and formation of new base pairs between the initiating ssDNA and the complementary strand within the duplex. Here, we used cryo-EM to solve the structures of human RAD51 in complex with DNA molecules, in presynaptic and postsynaptic states, at near-atomic resolution...
December 12, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27941861/warfarin-and-vitamin-k-compete-for-binding-to-phe55-in-human-vkor
#13
Katrin J Czogalla, Arijit Biswas, Klara Höning, Veit Hornung, Kerstin Liphardt, Matthias Watzka, Johannes Oldenburg
Vitamin K epoxide reductase (VKOR) catalyzes the reduction of vitamin K quinone and vitamin K 2,3-epoxide, a process essential to sustain γ-carboxylation of vitamin K-dependent proteins. VKOR is also a therapeutic target of warfarin, a treatment for thrombotic disorders. However, the structural and functional basis of vitamin K reduction and the antagonism of warfarin inhibition remain elusive. Here, we identified putative binding sites of both K vitamers and warfarin on human VKOR. The predicted warfarin-binding site was verified by shifted dose-response curves of specified mutated residues...
December 12, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27892932/reciprocal-regulation-of-carbon-monoxide-metabolism-and-the-circadian-clock
#14
Roman Klemz, Silke Reischl, Thomas Wallach, Nicole Witte, Karsten Jürchott, Sabrina Klemz, Veronika Lang, Stephan Lorenzen, Miriam Knauer, Steffi Heidenreich, Min Xu, Jürgen A Ripperger, Michael Schupp, Ralf Stanewsky, Achim Kramer
Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Feedback of metabolic signals, such as redox state, NAD(+)/NADH and AMP/ADP ratios, or heme, modulate circadian rhythms and thereby optimize energy utilization across the 24-h cycle. We show that rhythmic heme degradation, which generates the signaling molecule carbon monoxide (CO), is required for normal circadian rhythms as well as circadian metabolic outputs. CO suppresses circadian transcription by attenuating CLOCK-BMAL1 binding to target promoters...
November 28, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27870834/position-dependent-termination-and-widespread-obligatory-frameshifting-in-euplotes-translation
#15
Alexei V Lobanov, Stephen M Heaphy, Anton A Turanov, Maxim V Gerashchenko, Sandra Pucciarelli, Raghul R Devaraj, Fang Xie, Vladislav A Petyuk, Richard D Smith, Lawrence A Klobutcher, John F Atkins, Cristina Miceli, Dolph L Hatfield, Pavel V Baranov, Vadim N Gladyshev
The ribosome can change its reading frame during translation in a process known as programmed ribosomal frameshifting. These rare events are supported by complex mRNA signals. However, we found that the ciliates Euplotes crassus and Euplotes focardii exhibit widespread frameshifting at stop codons. 47 different codons preceding stop signals resulted in either +1 or +2 frameshifts, and +1 frameshifting at AAA was the most frequent. The frameshifts showed unusual plasticity and rapid evolution, and had little influence on translation rates...
November 21, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27870833/integrative-classification-of-human-coding-and-noncoding-genes-through-rna-metabolism-profiles
#16
Neelanjan Mukherjee, Lorenzo Calviello, Antje Hirsekorn, Stefano de Pretis, Mattia Pelizzola, Uwe Ohler
Pervasive transcription of the human genome results in a heterogeneous mix of coding RNAs and long noncoding RNAs (lncRNAs). Only a small fraction of lncRNAs have demonstrated regulatory functions, thus making functional lncRNAs difficult to distinguish from nonfunctional transcriptional byproducts. This difficulty has resulted in numerous competing human lncRNA classifications that are complicated by a steady increase in the number of annotated lncRNAs. To address these challenges, we quantitatively examined transcription, splicing, degradation, localization and translation for coding and noncoding human genes...
November 21, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27870832/position-effects-influence-hiv-latency-reversal
#17
Heng-Chang Chen, Javier P Martinez, Eduard Zorita, Andreas Meyerhans, Guillaume J Filion
The main obstacle to curing HIV is the presence of latent proviruses in the bodies of infected patients. The partial success of reactivation therapies suggests that the genomic context of integrated proviruses can interfere with treatment. Here we developed a method called Barcoded HIV ensembles (B-HIVE) to map the chromosomal locations of thousands of individual proviruses while tracking their transcriptional activities in an infected cell population. B-HIVE revealed that, in Jurkat cells, the expression of HIV is strongest close to endogenous enhancers...
November 21, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28054569/new-pieces-to-an-old-puzzle-identifying-the-warfarin-binding-site-that-prevents-clotting
#18
Jacob K Hilton, Wade D Van Horn
No abstract text is available yet for this article.
January 5, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28054568/single-virus-tracking-uncovers-the-missing-link-between-hiv-integration-site-location-and-viral-gene-expression
#19
Angela Ciuffi, Sara Cristinelli, Sylvie Rato
No abstract text is available yet for this article.
January 5, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28054567/break-induced-replication-an-unhealthy-choice-for-stress-relief
#20
Juraj Kramara, Beth Osia, Anna Malkova
No abstract text is available yet for this article.
January 5, 2017: Nature Structural & Molecular Biology
journal
journal
40509
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"