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Oligomerization

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https://www.readbyqxmd.com/read/28651250/a-role-for-neuronal-alpha-synuclein-in-gastrointestinal-immunity
#1
Ethan Stolzenberg, Deborah Berry, De Yang, Ernest Y Lee, Alexander Kroemer, Stuart Kaufman, Gerard C L Wong, Joost J Oppenheim, Supti Sen, Thomas Fishbein, Ad Bax, Brent Harris, Denise Barbut, Michael A Zasloff
BACKGROUND: Alpha-synuclein (αS) is a nerve cell protein associated with Parkinson disease (PD). Accumulation of αS within the enteric nervous system (ENS) and its traffic from the gut to the brain are implicated in the pathogenesis and progression of PD. αS has no known function in humans and the reason for its accumulation within the ENS is unknown. Several recent studies conducted in rodents have linked αS to immune cell activation in the central nervous system. We hypothesized that αS in the ENS might play a role in the innate immune defenses of the human gastrointestinal (GI) tract...
June 27, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28650691/changes-in-cartilage-biomarker-levels-during-a-transcontinental-multistage-footrace-over-4486-km
#2
Annegret Mündermann, Christopher Klenk, Christian Billich, Corina Nüesch, Geert Pagenstert, Arno Schmidt-Trucksäss, Uwe Schütz
BACKGROUND: Cartilage turnover and load-induced tissue changes are frequently assessed by quantifying concentrations of cartilage biomarkers in serum. To date, information on the effects of ultramarathon running on articular cartilage is scarce. HYPOTHESIS: Serum concentrations of cartilage oligomeric matrix protein (COMP), matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, COL2-3/4C long mono (C2C), procollagen type II C-terminal propeptide (CPII), and C2C:CPII will increase throughout a multistage ultramarathon...
June 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28650631/effect-of-the-biphenyl-neolignan-honokiol-on-a%C3%AE-42-induced-toxicity-in-caenorhabditis-elegans-a%C3%AE-42-fibrillation-cholinesterase-activity-dpph-radicals-and-iron-ii-chelation
#3
Srinivas Kantham, Stephen Chan, Gawain McColl, Jared Miles, Suresh Kumar Veliyath, Girdhar Singh Deora, Satish N Dighe, Samira Khabbazi, Marie-Odile Parat, Benjamin P Ross
The biphenyl neolignan honokiol is a neuroprotectant which has been proposed as a treatment for central nervous system disorders such as Alzheimer's disease (AD). The death of cholinergic neurons in AD is attributed to multiple factors, including: accumulation and fibrillation of amyloid beta peptide (Aβ) within the brain; metal ion toxicity; and oxidative stress. In this study, we used a transgenic Caenorhabditis elegans model expressing full length Aβ42 as a convenient in vivo system for examining the effect of honokiol against Aβ-induced toxicity...
June 26, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28650319/somatostatin-binds-to-the-human-amyloid-%C3%AE-peptide-and-favors-the-formation-of-distinct-oligomers
#4
Hansen Wang, Lisa D Muiznieks, Punam Ghosh, Declan Williams, Michael Solarski, Andrew Fang, Alejandro Ruiz-Riquelme, Régis Pomès, Joel C Watts, Avi Chakrabartty, Holger Wille, Simon Sharpe, Gerold Schmitt-Ulms
The amyloid β peptide (Aβ) is a key player in the etiology of Alzheimer disease (AD), yet a systematic investigation of its molecular interactions has not been reported. Here we identified by quantitative mass spectrometry proteins in human brain extract that bind to oligomeric Aβ1-42 (oAβ1-42) and/or monomeric Aβ1-42 (mAβ1-42) baits. Remarkably, the cyclic neuroendocrine peptide somatostatin-14 (SST14) was observed to be the most selectively enriched oAβ1-42 binder. The binding interface comprises a central tryptophan within SST14 and the N-terminus of Aβ1-42...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28649408/ser-thr-protein-kinase-prkc-mediated-regulation-of-groel-is-critical-for-biofilm-formation-in-bacillus-anthracis
#5
Gunjan Arora, Andaleeb Sajid, Richa Virmani, Anshika Singhal, C M Santosh Kumar, Neha Dhasmana, Tanya Khanna, Abhijit Maji, Richa Misra, Virginie Molle, Dörte Becher, Ulf Gerth, Shekhar C Mande, Yogendra Singh
PrkC is a conserved Ser/Thr protein kinase encoded in Bacillus anthracis genome. PrkC is shown to be important for B. anthracis pathogenesis, but little is known about its other functions and phosphorylated substrates. Systemic analyses indicate the compelling role of PrkC in phosphorylating multiple substrates, including the essential chaperone GroEL. Through mass spectrometry, we identified that PrkC phosphorylates GroEL on six threonine residues that are distributed in three canonical regions. Phosphorylation facilitates the oligomerization of GroEL to the physiologically active tetradecameric state and increases its affinity toward the co-chaperone GroES...
2017: NPJ Biofilms and Microbiomes
https://www.readbyqxmd.com/read/28649245/camelid-single-domain-antibodies-as-an-alternative-to-overcome-challenges-related-to-the-prevention-detection-and-control-of-neglected-tropical-diseases
#6
REVIEW
Carla F C Fernandes, Soraya Dos S Pereira, Marcos B Luiz, Juliana P Zuliani, Gilvan P Furtado, Rodrigo G Stabeli
Due mainly to properties such as high affinity and antigen specificity, antibodies have become important tools for biomedical research, diagnosis, and treatment of several human diseases. When the objective is to administer them for therapy, strategies are used to reduce the heterologous protein immunogenicity and to improve pharmacokinetic and pharmacodynamic characteristics. Size minimization contributes to ameliorate these characteristics, while preserving the antigen-antibody interaction site. Since the discovery that camelids produce functional antibodies devoid of light chains, studies have proposed the use of single domains for biosensors, monitoring and treatment of tumors, therapies for inflammatory and neurodegenerative diseases, drug delivery, or passive immunotherapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28648830/purinergic-p2y-receptors-molecular-diversity-and-implications-for-treatment-of-cardiovascular-diseases
#7
REVIEW
Akiyuki Nishimura, Caroline Sunggip, Sayaka Oda, Takuro Numaga-Tomita, Makoto Tsuda, Motohiro Nishida
Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes...
June 22, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28648608/structures-of-pgam5-provide-insight-into-active-site-plasticity-and-multimeric-assembly
#8
Apirat Chaikuad, Panagis Filippakopoulos, Sean R Marcsisin, Sarah Picaud, Martin Schröder, Shiori Sekine, Hidenori Ichijo, John R Engen, Kohsuke Takeda, Stefan Knapp
PGAM5 is a mitochondrial membrane protein that functions as an atypical Ser/Thr phosphatase and is a regulator of oxidative stress response, necroptosis, and autophagy. Here we present several crystal structures of PGAM5 including the activating N-terminal regulatory sequences, providing a model for structural plasticity, dimerization of the catalytic domain, and the assembly into an enzymatically active dodecameric form. Oligomeric states observed in structures were supported by hydrogen exchange mass spectrometry, size-exclusion chromatography, and analytical ultracentrifugation experiments in solution...
June 10, 2017: Structure
https://www.readbyqxmd.com/read/28646414/dynamic-meso-scale-anchorage-of-gpi-anchored-receptors-in-the-plasma-membrane-prion-protein-vs-thy1
#9
Yuri L Nemoto, Roger J Morris, Hiroko Hijikata, Taka A Tsunoyama, Akihiro C E Shibata, Rinshi S Kasai, Akihiro Kusumi, Takahiro K Fujiwara
The central mechanism for the transmission of the prion protein misfolding is the structural conversion of the normal cellular prion protein to the pathogenic misfolded prion protein, by the interaction with misfolded prion protein. This process might be enhanced due to the homo-dimerization/oligomerization of normal prion protein. However, the behaviors of normal prion protein in the plasma membrane have remained largely unknown. Here, using single fluorescent-molecule imaging, we found that both prion protein and Thy1, a control glycosylphosphatidylinositol-anchored protein, exhibited very similar intermittent transient immobilizations lasting for a few seconds within an area of 24...
June 24, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28646204/optogenetic-protein-clustering-through-fluorescent-protein-tagging-and-extension-of-cry2
#10
Hyerim Park, Na Yeon Kim, Sangkyu Lee, Nury Kim, Jihoon Kim, Won Do Heo
Protein homo-oligomerization is an important molecular mechanism in many biological processes. Therefore, the ability to control protein homo-oligomerization allows the manipulation and interrogation of numerous cellular events. To achieve this, cryptochrome 2 (CRY2) from Arabidopsis thaliana has been recently utilized for blue light-dependent spatiotemporal control of protein homo-oligomerization. However, limited knowledge on molecular characteristics of CRY2 obscures its widespread applications. Here, we identify important determinants for efficient cryptochrome 2 clustering and introduce a new CRY2 module, named ''CRY2clust'', to induce rapid and efficient homo-oligomerization of target proteins by employing diverse fluorescent proteins and an extremely short peptide...
June 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28644885/organic-anion-transporting-polypeptide-1b3-can-form-homo-and-hetero-oligomers
#11
Yuchen Zhang, Kelli H Boxberger, Bruno Hagenbuch
OATP1B3 is a 12 transmembrane domain protein expressed at the basolateral membrane of human hepatocytes where it mediates the uptake of numerous drugs and endogenous compounds. Previous western blot results suggest the formation of OATP1B3 multimers. In order to better understand the function of OATP1B3 under normal physiological conditions, we investigated its oligomerization status. We transiently transfected OATP1B3 with a C-terminal His-, FLAG- or HA-tag in HEK293 cells and used co-immunoprecipitation and a Proximity Ligation Assay to detect interactions between the different constructs...
2017: PloS One
https://www.readbyqxmd.com/read/28643473/can-the-propensity-of-protein-crystallization-be-increased-by-using-systematic-screening-with-metals
#12
REVIEW
Raghurama P Hegde, Pavithra G Chinnaswamy, Debayan Dey, Steven C Almo, S Ramakumar, Udupi A Ramagopal
Protein crystallization is one of the major bottlenecks in protein structure elucidation with new strategies being constantly developed to improve the chances of crystallization. Generally, well-ordered epitopes possessing complementary-surface and capable of producing stable inter-protein interactions generate a regular three-dimensional arrangement of protein molecules which eventually results in a crystal lattice. Metals, when used for crystallization, with their various coordination numbers and geometries, can generate such epitopes mediating protein oligomerization and/or establish crystal contacts...
June 23, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28643168/self-aggregation-of-synthetic-zinc-methyl-20-substituted-3-hydroxymethyl-pyropheophorbides-as-models-of-bacteriochlorophyll-c
#13
Ayaka Wada, Hitoshi Tamiaki
Zinc 3-hydroxymethyl-13(1)-oxo-chlorins bearing a variety of primary alkyl groups at the 20-position were prepared as models of bacteriochlorophyll-c by chemical modification of naturally occurring chlorophyll-a. The synthetic chlorophyll-a derivatives self-aggregated in an aqueous Triton X-100 solution to afford large oligomers whose Soret and Qy bands were red-shifted and broadened, compared with the bands of their monomers in tetrahydrofuran. The oligomeric bands are similar to those of bacteriochlorophyll-c self-aggregates in chlorosomes, the main light-harvesting antennae of photosynthetic green bacteria...
June 22, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28642958/phosphorylation-of-a-full-length-amyloid-%C3%AE-peptide-modulates-its-amyloid-aggregation-cell-binding-and-neurotoxic-properties
#14
Elaheh Jamasbi, Frances Separovic, Mohammed Akhter Hossain, Giuseppe Donato Ciccotosto
Amyloid beta peptide (Aβ) is the major protein component of the amyloid plaques that are present in the brains of Alzheimer's disease (AD) patients. Aβ42 peptide is a known neurotoxic agent that binds to neurons and, under specific aggregation conditions, triggers cell death. Aβ peptide can undergo specific amino acid posttranslational modifications, such as phosphorylation, that are important for modulating its proteolytic degradation, aggregation, binding to lipid membranes and neurotoxic functions. Peptides phosphorylated at serine 8 in full-length Aβ42 (pAβ42) were synthesised and compared to native Aβ42 peptide...
June 23, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28642041/interaction-of-polyhedral-oligomeric-silsesquioxanes-and-dipalmitoylphosphatidylcholine-at-the-air-water-interface-thermodynamic-and-rheological-study
#15
M Skrzypiec, G As Georgiev, M Rojewska, K Prochaska
Polyhedral oligomeric silsesquioxanes (POSS) derivatives containing open silsesquioxane cage bear great potential for biomedical applications and therefore their lateral interactions with phospholipids, major biomembranes and drug vehicles constituent, should be studied in detail. That is why the properties of surface films by two POSS-derivatives, POSS-polyethylene glycol (POSS-PEG) and POSS-perfluoroalkyl (POSS-OFP), pure and in presence of 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) were studied using Langmuir surface balance...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28642038/functional-characterization-of-21-allelic-variants-of-dihydropyrimidinase
#16
Eiji Hishinuma, Fumika Akai, Yoko Narita, Masamitsu Maekawa, Hiroaki Yamaguchi, Nariyasu Mano, Akifumi Oda, Noriyasu Hirasawa, Masahiro Hiratsuka
Dihydropyrimidinase (DHP, EC 3.5.2.2), encoded by the gene DPYS, is the second enzyme in the catabolic pathway of pyrimidine and of fluoropyrimidine drugs such as 5-fluorouracil, which are commonly used in anticancer treatment; DHP catalyzes the hydrolytic ring opening of dihydrouracil and dihydro-5-fluorouracil. DPYS mutations are known to contribute to interindividual variations in the toxicity of fluoropyrimidine drugs, but the functional characterization of DHP allelic variants remains inadequate. In this study, in vitro analysis was performed on 22 allelic variants of DHP by transiently expressing wild-type DHP and 21 DHP variants in 293FT cells and characterizing their enzymatic activities by using dihydrouracil and dihydro-5-fluorouracil as substrates...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28641977/a-novel-fluorescent-probe-reveals-starvation-controls-the-commitment-of-amyloid-precursor-protein-to-the-lysosome
#17
Leanne K Hein, Pirjo M Apaja, Kathryn Hattersley, Randall H Grose, Jianling Xie, Christopher G Proud, Timothy J Sargeant
Alzheimer's disease is the most important cause of dementia but there is no therapy that has been demonstrated to stop or slow disease progression. Amyloid precursor protein (APP) is the source of amyloid-β (Aβ), which aggregates in Alzheimer's disease to form toxic oligomeric species. The endo-lysosomal system can clear APP and Aβ from the cell if these molecular species are trafficked through to the lysosome. Currently, there are no easy methods available for the analysis of lysosomal APP trafficking. We therefore generated a fusion protein (tandem-fluorescent, or tf-APP) that allows detection of changes in APP trafficking using accessible techniques such as flow cytometry...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641441/the-closo-si12c12-molecule-from-cluster-to-crystal-effects-of-hydrogenation-and-oligomerization-on-excited-states
#18
Xiaofeng F Duan, Larry W Burggraf
Excited state properties of chain and cyclic oligomers of closo-Si12C12 moieties are calculated using time-dependent density functional theory methods. Ultraviolet, visible, and near-infrared photo-absorption properties are described for oligomers that form by linking closo-Si12C12 monomer moieties through Si-Si bonds. Natural transition orbitals for electron and hole states of stationary-state excitons in oligomers were compared to understand how exciton states are influenced by oligomer structure. Depending on the structure, some prominent excited states have large electron-hole charge separation while others do not; some exhibit exciton delocalization while others do not...
June 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28641007/palladium-catalyzed-sn2-cyclization-of-ambivalent-bromoalkadienyl-malonates-preparation-of-medium-to-large-membered-endocyclic-allenes
#19
Hiroaki Ichio, Hidetoshi Murakami, Yen-Chou Chen, Tamotsu Takahashi, Masamichi Ogasawara
A palladium-catalyzed reaction of preparing various endocyclic allenes was developed. The substrates for the reaction were readily available ω-(pronucleophile-tethered)-3-bromo-1,3-alkadienes, and a palladium-catalyst facilitated their unimolecular SN2'-cyclization in the presence of potassium tert-butoxide to give the corresponding 9- to 16-membered endocyclic allenes in fair yields of up to 67% together with the dimeric 16- to 32-membered endocyclic bis-allenes and other oligomeric/polymeric intermolecular reaction products...
June 22, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28640593/dna-condensation-induced-by-a-star-shaped-hexameric-cationic-surfactant
#20
Yaxun Fan, Hua Wang, Chengqian He, Fulin Qiao, Shu Wang, Yilin Wang
The interactions between a star-shaped hexameric cationic quaternary ammonium surfactant PAHB and calf thymus DNA and induced DNA condensation were investigated by ζ-potential, dynamic light scattering, atomic force microscopy, isothermal titration calorimetry, ethidium bromide exclusion assay, circular dichroism and cytotoxicity assay. With the addition of PAHB, long extended DNA molecules exhibit successive conformational transitions from elongated coil to partially condensed cluster-like aggregate, globules-on-a-string structure, and then to fully condensed globule until the saturation point of interaction between PAHB and DNA, which is slightly above their charge neutralization point...
June 22, 2017: ACS Applied Materials & Interfaces
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