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Journal of Molecular Biology

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https://www.readbyqxmd.com/read/30227136/multiscale-molecular-visualization
#1
REVIEW
Haichao Miao, Tobias Klein, David Kořil, Peter Mindek, Karsten Schatz, M Eduard Gröller, Barbora Kozlíková, Tobias Isenberg, Ivan Viola
We provide a high-level survey of multiscale molecular visualization techniques, with a focus on application-domain questions, challenges, and tasks. We provide a general introduction to molecular visualization basics and describe a number of domain-specific tasks that drive this work. These tasks, in turn, serve as the general structure of the following survey. First we discuss methods that support the visual analysis of molecular dynamics simulations. We discuss, in particular, visual abstraction and temporal aggregation...
September 15, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30227135/multiple-parameters-drive-the-efficiency-of-crispr-cas9-induced-gene-modifications-in-yarrowia-lipolytica
#2
Vinciane Borsenberger, Djamila Onésime, Delphine Lestrade, Coraline Rigouin, Cécile Neuvéglise, Fayza Daboussi, Florence Bordes
Yarrowia lipolytica is an oleaginous yeast of growing industrial interest for biotechnological applications. In the last few years, genome edition has become an easier and more accessible prospect with the world wild spread development of CRISPR/Cas9 technology. In this study we focused our attention on the production of the two key elements of the CRISPR-Cas9 RiboNucleic acid Protein complex in this non-conventional yeast. The efficiency of NHEJ induced knock out was measured by time-course monitoring using multiple parameters flow cytometry, as well as phenotypic and genotypic observations, and linked to nuclease production levels showing that its strong overexpression is unnecessary...
September 15, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30227134/serine-integrase-attp-binding-and-specificity
#3
Huiguang Li, Robert Sharp, Karen Rutherford, Kushol Gupta, Gregory D Van Duyne
Serine integrases catalyze the site-specific insertion of viral DNA into a host's genome. The minimal requirements and irreversible nature of this integration reaction has led to the use of serine integrases in applications ranging from bacterial memory storage devices to gene therapy. Our understanding of how the integrase proteins recognize the viral (attP) and host (attB) attachment sites is limited, with structural data available for only a Listeria integrase C-terminal domain (CTD) bound to an attP half-site...
September 15, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30220583/corrigendum-to-a-catalytically-disabled-double-mutant-of-src-tyrosine-kinase-can-be-stabilized-into-an-active-like-conformation-j-mol-biol-430-6-mar-16-2018-881-889
#4
Yilin Meng, Lalima G Ahuja, Alexandr P Kornev, Susan S Taylor, Benoît Roux
No abstract text is available yet for this article.
September 13, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30213727/phase-seperation
#5
EDITORIAL
Julie D Forman-Kay, Richard W Kriwacki, Geraldine Seydoux
No abstract text is available yet for this article.
September 10, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30213726/a-sortase-a-programmable-phage-display-format-for-improved-panning-of-fab-antibody-libraries
#6
Henry D Wilson, Xiuling Li, Haiyong Peng, Christoph Rader
Phage display of combinatorial antibody libraries is a versatile tool in the field of antibody engineering, with diverse applications including monoclonal antibody (mAb) discovery, affinity maturation, and humanization. To improve the selection efficiency of antibody libraries, we developed a new phagemid display system that addresses the complication of bald phage propagation. The phagemid facilitates the biotinylation of Fab antibody fragments displayed on phage via Sortase A catalysis, and the subsequent enrichment of Fab-displaying phage during selections...
September 10, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30205092/structural-basis-of-epitope-recognition-by-heavy-chain-camelid-antibodies
#7
Uroš Zavrtanik, Junoš Lukan, Remy Loris, Jurij Lah, San Hadži
Truncated versions of heavy chain antibodies (HCAbs) from camelids, also termed nanobodies, comprise only one-tenth the mass of conventional antibodies, yet retain similar, high binding affinities for the antigens. Here we analyze a large dataset of nanobody-antigen crystal structures and investigate how nanobody-antigen recognition compares to the one by conventional antibodies. We find that nanobody paratopes are enriched in aromatic residues just like conventional antibodies, but additionally they also bear a more hydrophobic character...
September 8, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30201267/dynamic-interplay-of-rna-and-protein-in-the-human-immunodeficiency-virus-1-reverse-transcription-initiation-complex
#8
Aaron T Coey, Kevin P Larsen, Junhong Choi, Daniel J Barrero, Joseph D Puglisi, Elisabetta Viani Puglisi
The initiation of reverse transcription in human immunodeficiency virus-1 (HIV-1) is a key early step in the virus replication cycle. During this process, the viral enzyme reverse transcriptase (RT) copies the single-stranded viral RNA (vRNA) genome into double-stranded DNA using human tRNALys 3 as a primer for initiation. The tRNA primer and vRNA genome contain several complementary sequences that are important for regulating reverse transcription initiation kinetics. Using single-molecule Förster resonance energy transfer (smFRET) spectroscopy, we demonstrate that the vRNA-tRNA initiation complex is conformationally heterogeneous and dynamic in the absence of RT...
September 7, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30194969/molecular-basis-for-immunity-protein-recognition-of-a-type-vii-secretion-system-exported-antibacterial-toxin
#9
Timothy A Klein, Manuel Pazos, Michael G Surette, Waldemar Vollmer, John C Whitney
Gram-positive bacteria deploy the type VII secretion system (T7SS) to facilitate interactions between eukaryotic and prokaryotic cells. In recent work, we identified the TelC protein from Streptococcus intermedius as a T7SS-exported lipid II phosphatase that mediates interbacterial competition. TelC exerts toxicity in the inner wall zone of Gram-positive bacteria; however, intercellular intoxication of sister cells does not occur because they express the TipC immunity protein. In the present study, we sought to characterize the molecular basis of self-protection by TipC...
September 5, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30193985/crispr-cas-complex-functional-networks-and-multiple-roles-beyond-adaptive-immunity
#10
REVIEW
Guilhem Faure, Kira S Makarova, Eugene V Koonin
CRISPR-Cas is a prokaryotic adaptive immune system that functions by incorporating fragments of foreign DNA into CRISPR arrays. The arrays containing spacers derived from foreign DNA are transcribed, and the transcripts are processed to generate spacer-containing mature CRISPR-RNAs that are employed as guides to specifically recognize and cleave the DNA or RNA of the cognate parasitic genetic elements. The CRISPR-Cas systems show remarkable complexity and diversity of molecular organization and appear to be involved in various cellular functions that are distinct from, even if connected to, adaptive immunity...
September 5, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30193986/structural-plasticity-of-neurexin-1%C3%AE-implications-for-its-role-as-synaptic-organizer
#11
Jianfang Liu, Anurag Misra, Sekhar Reddy, Mark Andrew White, Gang Ren, Gabby Rudenko
α-Neurexins are synaptic organizing molecules implicated in neuropsychiatric disorders. They bind and arrange an array of different partners in the synaptic cleft. The extracellular region of neurexin 1α (n1α) contains six LNS domains (L1-L6) interspersed by three Egf-like repeats. N1α must encode highly evolved structure-function relationships in order to fit into the narrow confines of the synaptic cleft, and also recruit its large, membrane-bound partners. Internal molecular flexibility could provide a solution, however, it is challenging to delineate because currently no structural methods permit high resolution structure determination of large, flexible, multi-domain protein molecules...
September 4, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30189201/oligomerization-and-auto-methylation-of-the-human-lysine-methyltransferase-setd6
#12
Lital Estrella Weil, Yulia Shmidov, Margarita Kublanovsky, David Morgenstern, Michal Feldman, Ronit Bitton, Dan Levy
Signaling via lysine methylation by protein lysine methyltransferases (PKMTs), has been linked to diverse biological and disease processes. The mono-methyltransferase SETD6 (SET-domain-containing protein 6) is a member of the PKMT family and was previously shown to regulate essential cellular processes such as the NF-κB, WNT and the oxidative stress pathways. Yet, on the biochemical level, little is known about the enzymatic mode of action of SETD6. Here we provide evidence that SETD6 forms high molecular weight structures...
September 3, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30189200/molecular-basis-of-class-iii-ligand-recognition-by-pdz3-in-murine-protein-tyrosine-phosphatase-ptpn13
#13
Gerd Kock, Markus Dicks, King Tuo Yip, Bastian Kohl, Stefanie Pütz, Rolf Heumann, Kai S Erdmann, Raphael Stoll
Protein tyrosine phosphatase PTPN13, also known as PTP-BL in mice, represents a large multi domain non-transmembrane scaffolding protein that contains five consecutive PDZ domains. Here, we report the solution structures of the extended murine PTPN13 PDZ3 domain in its apo form and in complex with its physiological ligand, the carboxy-terminus of PRK2, determined by multidimensional NMR spectroscopy. Both in its ligand-free state and when complexed to PRK2, PDZ3 of PTPN13 adopts the classical compact, globular D/E fold...
September 3, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30179605/a-cis-acting-element-downstream-of-the-mouse-mammary-tumor-virus-major-splice-donor-critical-for-rna-elongation-and-stability
#14
Shaima Akhlaq, Pretty S Philip, Lizna M Ali, Jaquelin P Dudley, Tahir A Rizvi, Farah Mustafa
BACKGROUND: The mouse mammary tumor virus (MMTV) encodes a functional signal peptide (SP), a cleavage product of envelope and Rem proteins. SP interacts with a 3' cis-acting RNA element, the Rem-responsive element (RmRE), to facilitate expression of both unspliced genomic (gRNA) and spliced mRNAs. An additional RmRE, has been proposed at the 5' end of the genome, facilitating nuclear export of the unspliced gRNA, whereas the 3' RmRE could facilitate translation of all other mRNAs, including gRNA...
September 1, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30176245/structural-analysis-of-the-arabidopsis-al2-pal-and-prc1-complex-provides-mechanistic-insight-about-active-to-repressive-chromatin-state-switch
#15
Ling Peng, Longlong Wang, Yingpei Zhang, Aiwu Dong, Wen-Hui Shen, Ying Huang
Polycomb Group (PcG) proteins play essential roles in transcriptional gene repression during both animal and plant development. Polycomb Repression Complex 1 (PRC1) is one of the key functional modules in PcG silencing. It acts as both a reader of H3K27me3 (histone H3 lysine 27 trimethylation) and a writer of H2Aub1 (histone H2A monoubiquitination) in establishing stable repression chromatin state. Intriguingly, a recent study showed that Arabidopsis PRC1 contains the H3K4me3-binding proteins of the ALFIN-like (AL) family, pointing to a chromatin state switch from active to repressive transcription of embryonic genes required for vegetative plant development...
August 31, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30171840/regulation-of-uvrd-helicase-activity-by-mutl
#16
Yerdos A Ordabayev, Binh Nguyen, Anita Niedziela-Majka, Timothy M Lohman
Escherichia coli UvrD is a superfamily 1 helicase/translocase involved in multiple DNA metabolic processes including methyl-directed mismatch DNA repair. Although a UvrD monomer can translocate along single-stranded DNA, a UvrD dimer is needed for processive helicase activity in vitro. E. coli MutL, a regulatory protein involved in methyl-directed mismatch repair, stimulates UvrD helicase activity; however, the mechanism is not well understood. Using single-molecule fluorescence and ensemble approaches, we find that a single MutL dimer can activate latent UvrD monomer helicase activity...
August 30, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30171839/ursodeoxycholic-acid-improves-mitochondrial-function-and-redistributes-drp1-in-fibroblasts-from-patients-with-either-sporadic-or-familial-alzheimer-s-disease
#17
Simon M Bell, Katy Barnes, Hannah Clemmens, Aziza R Al-Rafiah, Ebtisam A Al-Ofi, Vicki Leech, Oliver Bandmann, Pamela J Shaw, Daniel J Blackburn, Laura Ferraiuolo, Heather Mortiboys
Alzheimer's disease (AD) is the leading cause of dementia worldwide. Mitochondrial abnormalities have been identified in many cell types in AD, with deficits preceding the development of the classical pathological aggregations. Ursodeoxycholic acid (UDCA), a treatment for primary biliary cirrhosis, improves mitochondrial function in fibroblasts derived from Parkinson's disease patients as well as several animal models of AD and Parkinson's disease. In this paper, we investigated both mitochondrial function and morphology in fibroblasts from patients with both sporadic and familial AD...
August 29, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30170006/molecular-biology-meets-the-learning-sciences-visualizations-in-education-and-outreach
#18
REVIEW
Jodie Jenkinson
Scientific visualizations (illustrations, three-dimensional models, animations, simulations, etc.) play an essential role in biology education, particularly when it comes to communicating phenomena occurring at the submicroscopic levels, beyond the level of unaided observation and without comparable counterparts at the macroscopic level. Students struggle with understanding the sizes of cells, molecules, and atoms in relation to one another as well as differentiating between the various time scales within which each of these levels is functioning...
August 29, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30170005/nanodisc-forming-scaffold-protein-promoted-retardation-of-amyloid-beta-aggregation
#19
Bikash Ranjan Sahoo, Takuya Genjo, Sarah J Cox, Andrea K Stoddard, G M Anantharamaiah, Carol Fierke, Ayyalusamy Ramamoorthy
Peptidic-nanodiscs are useful membrane-mimetic tools for structural and functional studies of membrane proteins, and membrane interacting peptides including amyloids. Here, we demonstrate anti-amyloidogenic activities of a nanodisc-forming 18-residue peptide (denoted as 4F), both in lipid-bound and lipid-free states by using Alzheimer's amyloid-beta (Aβ40) peptide as an example. Fluorescence based amyloid fibrillation kinetic assays showed a significant delay in Aβ40 amyloid aggregation by the 4F peptide...
August 28, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30153436/carm1-prmt4-acts-as-a-transcriptional-coactivator-during-retinoic-acid-induced-embryonic-stem-cell-differentiation
#20
Cynthia M Quintero, Kristian B Laursen, Nigel P Mongan, Minkui Luo, Lorraine J Gudas
Activation of the retinoic acid (RA) signaling pathway is important for controlling embryonic stem cell differentiation and development. Modulation of this pathway occurs through the recruitment of different epigenetic regulators at the retinoic acid receptors (RARs) located at RA-responsive elements and/or RA-responsive regions of RA-regulated genes. Coactivator-associated arginine methyltransferase 1 (CARM1, PRMT4) is a protein arginine methyltransferase that also functions as a transcriptional coactivator...
August 25, 2018: Journal of Molecular Biology
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