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https://www.readbyqxmd.com/read/29925026/cargos-rotate-at-microtubule-intersections-during-intracellular-trafficking
#1
Yuan Gao, Stephen M Anthony, Yanqi Yu, Yi Yi, Yan Yu
Intracellular cargos are transported by molecular motors along actin and microtubules, but how their dynamics depends on the complex structure of the cytoskeletal network remains unclear. In this study, we investigated this longstanding question by measuring simultaneously the rotational and translational dynamics of cargos at microtubule intersections in living cells. We engineered two-faced particles that are fluorescent on one hemisphere and opaque on the other and used their optical anisotropy to report the rotation of cargos...
June 19, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29925021/gating-currents-in-the-hv1-proton-channel
#2
Victor De La Rosa, Ian Scott Ramsey
The Hv1 proton channel shares striking structural homology with fourth transmembrane helical segment-type voltage-sensor (VS) domains but manifests distinctive functional properties, including a proton-selective "aqueous" conductance and allosteric control of voltage-dependent gating by changes in the transmembrane pH gradient. The mechanisms responsible for Hv1's functional properties remain poorly understood, in part because methods for measuring gating currents that directly report VS activation have not yet been described...
June 19, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29925020/redox-modulation-of-oligomeric-state-in-proline-utilization-a
#3
David A Korasick, Ashley C Campbell, Shelbi L Christgen, Srinivas Chakravarthy, Tommi A White, Donald F Becker, John J Tanner
Homooligomerization of proline utilization A (PutA) bifunctional flavoenzymes is intimately tied to catalytic function and substrate channeling. PutA from Bradyrhizobium japonicum (BjPutA) is unique among PutAs in that it forms a tetramer in solution. Curiously, a dimeric BjPutA hot spot mutant was previously shown to display wild-type catalytic activity despite lacking the tetrameric structure. These observations raised the question of what is the active oligomeric state of BjPutA. Herein, we investigate the factors that contribute to tetramerization of BjPutA in vitro...
June 19, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29925019/refinement-of-peptide-conformational-ensembles-by-2d-ir-spectroscopy-application-to-ala%C3%A2-ala%C3%A2-ala
#4
Chi-Jui Feng, Balamurugan Dhayalan, Andrei Tokmakoff
Characterizing ensembles of intrinsically disordered proteins is experimentally challenging because of the ill-conditioned nature of ensemble determination with limited data and the intrinsic fast dynamics of the conformational ensemble. Amide I two-dimensional infrared (2D IR) spectroscopy has picosecond time resolution to freeze structural ensembles as needed for probing disordered-protein ensembles and conformational dynamics. Also, developments in amide I computational spectroscopy now allow a quantitative and direct prediction of amide I spectra based on conformational distributions drawn from molecular dynamics simulations, providing a route to ensemble refinement against experimental spectra...
June 19, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29925017/thermodynamics-of-conformational-transitions-in-a-disordered-protein-backbone-model
#5
Justin A Drake, B Montgomery Pettitt
Conformational entropy is expected to contribute significantly to the thermodynamics of structural transitions in intrinsically disordered proteins or regions in response to protein/ligand binding, posttranslational modifications, and environmental changes. We calculated the backbone (dihedral) conformational entropy of oligoglycine (GlyN ), a protein backbone mimic and model intrinsically disordered region, as a function of chain length (N=3, 4, 5, 10, and 15) from simulations using three different approaches...
June 19, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29925008/comprehensive-quantification-of-the-modified-proteome-reveals-oxidative-heart-damage-in-mitochondrial-heteroplasmy
#6
Navratan Bagwan, Elena Bonzon-Kulichenko, Enrique Calvo, Ana Victoria Lechuga-Vieco, Spiros Michalakopoulos, Marco Trevisan-Herraz, Iakes Ezkurdia, José Manuel Rodríguez, Ricardo Magni, Ana Latorre-Pellicer, José Antonio Enríquez, Jesús Vázquez
Post-translational modifications hugely increase the functional diversity of proteomes. Recent algorithms based on ultratolerant database searching are forging a path to unbiased analysis of peptide modifications by shotgun mass spectrometry. However, these approaches identify only one-half of the modified forms potentially detectable and do not map the modified residue. Moreover, tools for the quantitative analysis of peptide modifications are currently lacking. Here, we present a suite of algorithms that allows comprehensive identification of detectable modifications, pinpoints the modified residues, and enables their quantitative analysis through an integrated statistical model...
June 19, 2018: Cell Reports
https://www.readbyqxmd.com/read/29924982/a-modified-pectic-polysaccharide-from-turmeric-curcuma-longa-with-antiulcer-effects-via-anti-secretary-mucoprotective-and-il-10-mediated-anti-inflammatory-mechanisms
#7
Harsha Mysore Rajagopal, Srikanta Belagihalli Manjegowda, Chandraprakash Serkad, Shylaja Mallaiah Dharmesh
Antiulcer potency of structurally defined low molecular weight modified pectin from turmeric (MTrPP) including inhibitory effects on H. pylori has been demonstrated previously by us. Given that ulcer is a disorder characterized by inflammatory responses leading to initiation, aggravation and perpetuation of disease conditions, the present study aims to understand the possible anti-inflammatory mechanisms through which MTrPP delivered antiulcer effects. Rats triggered with early phase gastric inflammation (LPS) followed by ulcer induction (swim-stress) were pretreated with MTrPP (150 mg/kg b...
June 17, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29924964/continuous-interdomain-orientation-distributions-reveal-components-of-binding-thermodynamics
#8
Yang Qi, Jeffrey W Martin, Adam W Barb, François Thélot, Anthony Yan, Bruce R Donald, Terrence G Oas
The flexibility of biological macromolecules is an important structural determinant of function. Unfortunately, the correlations between different motional modes are poorly captured by discrete ensemble representations. Here, we present new ways to both represent and visualize correlated interdomain motions. Interdomain motions are determined directly from residual dipolar couplings (RDCs), represented as a continuous conformational distribution, and visualized using the disk-on-sphere (DoS) representation...
June 17, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29924908/heterocyclic-analogs-of-sulforaphane-trigger-dna-damage-and-impede-dna-repair-in-colon-cancer-cells-interplay-of-hats-and-hdacs
#9
Adaobi Okonkwo, Joy Mitra, Gavin S Johnson, Li Li, Wan Mohaiza Dashwood, Muralidhar Hegde, Chen Yue, Roderick H Dashwood, Praveen Rajendran
SCOPE: DNA repair inhibitors have broad clinical applications in tumor types with DNA repair defects, including colorectal cancer. Structural analogs of the anticancer agent sulforaphane (SFN) were investigated as modifiers of histone deacetylase (HDAC) and histone acetyltransferase (HAT) activity, and for effects on DNA damage/repair pertinent to human colorectal cancer. METHODS AND RESULTS: In the polyposis in rat colon (Pirc) model, single oral administration of SFN and structurally-related long-chain isothiocyanates (ITCs) decreased HDAC3 expression and increased pH2AX levels markedly in adenomatous colon polyps, extending our prior observations on HDAC3 inhibition/turnover in cell-based assays...
June 20, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29924885/mono-and-bivalent-14-3-3-inhibitors-for-characterizing-supramolecular-lysine-wrapping-of-oligoethylene-glycol-oeg-moieties-in-proteins
#10
Elvan Yilmaz, David Bier, Xavier Guillory, Jeroen Briels, Yasser Ruiz-Blanco, Elsa Sanchez-Garcia, Christian Ottmann, Markus Kaiser
Previous studies have indicated the presence of defined interactions between oligo or poly(ethylene glycol) (OEG or PEG) and lysine residues. In these interactions, the OEG or PEG residues 'wrap around' the lysine amino group, thereby enabling complexation of the amino group by the ether oxygen residues. The resulting biochemical binding affinity and thus biological relevance of this supramolecular interaction however remains unclear so far. Here, we report that OEG-containing phosphophenol ether inhibitors of 14-3-3 proteins also display such a 'lysine-wrapping' binding mode...
June 20, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29924858/chemoenzymatic-synthesis-of-sialylated-lactuloses-and-their-inhibitory-effects-on-staphylococcus-aureus
#11
Jie Zeng, Yajie Hu, Tian Jia, Ruiyao Zhang, Tongchao Su, Junliang Sun, Haiyan Gao, Guanglei Li, Meng Cao, Mengdi Song
BACKGROUND: Sialylated glycoconjugates play important roles in physiological and pathological processes. However, available sialylated oligosaccharides source is limited which is a barrier to study their biological roles. This work reports an efficient approach to produce sialic acid-modified lactuloses and investigates their inhibitory effects on Staphylococcus aureus (S. aureus). METHODS: A one-pot two-enzyme (OPTE) sialylation system was used to efficiently synthesize sialylated lactuloses...
2018: PloS One
https://www.readbyqxmd.com/read/29924847/protein-dynamic-communities-from-elastic-network-models-align-closely-to-the-communities-defined-by-molecular-dynamics
#12
Sambit Kumar Mishra, Robert L Jernigan
Dynamic communities in proteins comprise the cohesive structural units that individually exhibit rigid body motions. These can correspond to structural domains, but are usually smaller parts that move with respect to one another in a protein's internal motions, key to its functional dynamics. Previous studies emphasized their importance to understand the nature of ligand-induced allosteric regulation. These studies reported that mutations to key community residues can hinder transmission of allosteric signals among the communities...
2018: PloS One
https://www.readbyqxmd.com/read/29924730/selective-bh3-mimetics-targeting-bcl-2-bcl-xl-or-mcl-1-induce-severe-mitochondrial-perturbations
#13
Kristina Henz, Aoula Al-Zebeeby, Marion Basoglu, Simone Fulda, Gerald M Cohen, Shankar Varadarajan, Meike Vogler
Induction of apoptosis by selective BH3-mimetics is currently investigated as a novel strategy for cancer treatment. Here, we report that selective BH3-mimetics induce apoptosis in a variety of hematological malignancies. Apoptosis is accompanied by severe mitochondrial toxicities upstream of caspase activation. Specifically, the selective BH3-mimetics ABT-199, A-1331852 and S63845, which target BCL-2, BCL-XL and MCL-1, respectively, induce comparable ultrastructural changes including mitochondrial swelling, a decrease of mitochondrial matrix density and severe loss of cristae structure...
June 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29924628/on-the-behavior-of-most-widely-spread-lipids-in-isotropic-bicelles
#14
Erik F Kot, Alexander Sergeevich Arseniev, Konstantin S Mineev
Isotropic bicelles are a widely used membrane mimetic for structural studies of membrane proteins and their transmembrane domains. Simple and cheap in preparation, they contain a patch of lipid bilayer that reproduces the native environment of membrane proteins. Despite the obvious power of bicelles in reproducing the various kinds of environments, the vast majority of structural studies employ the single lipid/detergent system. On the other hand, even if the alternative bicelle composition is used, the properties of mixtures are not characterized and the mere presence of lipid bilayer and discoidal shape of bicelle particles is not confirmed...
June 20, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29924600/amino-acid-selective-13-c-labeling-and-13-c-scrambling-profile-analysis-of-protein-%C3%AE-and-side-chain-carbons-in-escherichia-coli-utilized-for-protein-nuclear-magnetic-resonance
#15
Toshihiko Sugiki, Kyoko Furuita, Toshimichi Fujiwara, Chojiro Kojima
Amino acid selective isotope labeling is an important nuclear magnetic resonance technique, especially for larger proteins, providing strong bases for the unambiguous resonance assignments and information concerning the structure, dynamics, and intermolecular interactions. Amino acid selective 15 N labeling suffers from isotope dilution caused by metabolic interconversion of the amino acids, resulting in isotope scrambling within the target protein. Carbonyl 13 C atoms experience less isotope scrambling than the main-chain 15 N atoms do...
June 20, 2018: Biochemistry
https://www.readbyqxmd.com/read/29924590/a-vinylogous-photocleavage-strategy-allows-direct-photocaging-of-backbone-amide-structure
#16
Alicia E Mangubat-Medina, Samuel C Martin, Kengo Hanaya, Zachary T Ball
Side-chain modifications that respond to external stimuli provide a convenient approach to control macromolecular structure and function. Responsive modification of backbone amide structure represents a direct and powerful alternative to impact folding and function. Here, we describe a new photocaging method using histidine-directed backbone modification to selectively modify peptides and proteins at the amide N-H bond. A new vinylogous photocleavage method allows photorelease of the backbone modification and with it, restoration of function...
June 20, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29924502/crucial-role-of-protein-oligomerization-in-the-pathogenesis-of-alzheimer-s-and-parkinson-s-diseases
#17
REVIEW
Minee L Choi, Sonia Gandhi
Misfolding and aggregation of the proteins amyloid-β (Aβ), tau and alpha-synuclein (α-syn) is the predominant pathology underlying the neurodegenerative disorders, Alzheimer's and Parkinson's disease. Whilst end stage insoluble products of aggregation have been well characterised in human and animal models of disease, accumulating evidence from biophysical, cellular and in vivo studies has shown that soluble intermediates of aggregation, or oligomers, may be the key species that mediate toxicity and underlie seeding and spreading in disease...
June 20, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29924384/glycans-in-stem-cell-regulation-from-drosophila-tissue-stem-cells-to-mammalian-pluripotent-stem-cells
#18
REVIEW
Shoko Nishihara
Cell surface glycans, which are tissue-specific and developmentally regulated, work as essential modulators in ligand-receptor interactions, binding to various signal ligands including Wnt, Hedgehog, fibroblast growth factors, epidermal growth factors, and bone morphogenetic proteins, as well as in cell-cell interactions and cell-extracellular matrix interactions. These signals are essential for the stemness and differentiation of various kinds of stem cells. In addition, the intracellular O-linked N-acetylglucosamine, a form of glycosylation found only on nuclear or cytoplasmic proteins, regulates core transcription factors of stemness and phosphorylation of downstream signal components...
June 20, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29924345/recurrent-amplification-of-the-heterochromatin-protein-1-hp1-gene-family-across-dipter
#19
Quentin Helleu, Mia T Levine
The heterochromatic genome compartment mediates strictly conserved cellular processes such as chromosome segregation, telomere integrity, and genome stability. Paradoxically, heterochromatic DNA sequence is wildly unconserved. Recent reports that many hybrid incompatibility genes encode heterochromatin proteins, together with the observation that inter-species hybrids suffer aberrant heterochromatin-dependent processes, suggest that heterochromatic DNA packaging requires species-specific innovations. Testing this model of co-evolution between fast-evolving heterochromatic DNA and its packaging proteins begins with defining the latter...
June 19, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29924333/the-complete-mitochondrial-genome-of-ugyops-sp-hemiptera-delphacidae
#20
Fang Yu, Ai-Ping Liang
The complete mitochondrial genome (mitogenome) of Ugyops sp. (Hemiptera: Delphacidae) was sequenced, making it the first determined mitogenome from the subfamily Asiracinae, the basal clade of the family Delphacidae. The mitogenome was 15,259 bp in length with A + T content of 77.65% and contained 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a control region. The gene order was identical with that of the ancestral insect. The nucleotide composition analysis indicated that the whole mitogenome was strongly A-skewed (0...
May 1, 2018: Journal of Insect Science
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