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Oligomerization

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https://www.readbyqxmd.com/read/29676918/template-assisted-proximity-for-oligomerization-of-fullerenes
#1
Kum-Yi Cheng, Shern-Long Lee, Ting-Yang Kuo, Chih-Hsun Lin, Yen-Chen Chen, Ting-Hao Kuo, Cheng-Chih Hsu, Chun-Hsien Chen
Demonstrated herein is an unprecedented porous template-assisted reaction at the solid-liquid interface involving bond formation, which is typically collision-driven and occurs in the solution and gas phases. The template is a TMA (trimesic acid) monolayer with two-dimensional pores that host fullerenes, which otherwise exhibit an insignificant affinity to an undecorated graphite substrate. The confinement of C84 units in the TMA pores formulates a proximity that is ideal for bond formation. The oligomerization of C84 is triggered by an electric pulse via an STM (scanning tunneling microscope) tip...
April 20, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29676852/asp-58-modulates-lens-%C3%AE-a-crystallin-oligomer-formation-and-chaperone-function
#2
Takumi Takata, Tooru Nakamura-Hirota, Rintaro Inoue, Ken Morishima, Nobuhiro Sato, Masaaki Sugiyama, Noriko Fujii
Senile cataract onset is caused by insolubilization of lens proteins. The lens crystallin protein family correctly orders the formation of homo- or hetero-oligomers in lens fiber cells. Because lens fiber cells do not divide, covalent post-translational modifications such as isomerization of aspartate residues, accumulate with aging. Although many isomerization sites of αA-crystallin have been reported, their structural and functional contributions have never been identified. In this study, αA-crystallin was extracted from the aged human lens and separated into each oligomeric state by size exclusion chromatography and electrophoresis...
April 20, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29676567/biomolecular-corona-dictates-a%C3%AE-fibrillation-process
#3
Alireza Lotfabadi, Mohammad Javad Hajipour, Hossein Derakhshankhah, Afshin Peirovi, Samaneh Saffar, Elnaz Shams, Elnaz Fatemi, Ebrahim Barzegari, Sajad Sarvari, Faezeh Moakedi, Maryam Ferdousi, Fatemeh Atyabi, Ali Akbar Saboury, Rassoul Dinarvand
Amyloid beta (Aβ), which forms toxic oligomers and fibrils in brain tissues of patients with Alzheimer's disease, is broadly used as a model protein to probe the effect of nanoparticles (NPs) on oligomerization and fibrillation process. However, majority of the reports in the field, ignored the effect of biomolecular corona on the fibrillogenesis of the Aβ proteins. Biomolecular corona, which is a layer composed of various types of biomolecules that covers surface of NPs upon their interaction with biological fluids, determines the biological fates of NPs...
April 20, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29676021/detection-of-alpha-synuclein-conformational-variants-from-gastro-intestinal-biopsy-tissue-as-a-potential-biomarker-for-parkinson-s-disease
#4
Claudio Ruffmann, Nora Bengoa-Vergniory, Ilaria Poggiolini, Diane Ritchie, Michele T Hu, Javier Alegre-Abarrategui, Laura Parkkinen
AIMS: Gastrointestinal (GI) α-synuclein (aSyn) detection as a potential biomarker of Parkinson's disease (PD) is challenged by conflicting results of recent studies. To increase sensitivity and specificity, we applied three techniques to detect different conformations of aSyn in GI biopsies obtained from a longitudinal, clinically well-characterized cohort of PD patients and healthy controls (HC). METHODS: With immunohistochemistry (IHC), we used antibodies reactive for total, phosphorylated and oligomeric aSyn; with aSyn proximity ligation assay (AS-PLA), we targeted oligomeric aSyn species specifically; and with paraffin-embedded tissue blot (AS-PET-blot) we aimed to detect fibrillary, synaptic aSyn...
April 19, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29675582/multifunctional-opioid-ligands
#5
Jessica P Anand, Deanna Montgomery
The opioid receptor system plays a major role in the regulation of mood, reward, and pain. The opioid receptors therefore make attractive targets for the treatment of many different conditions, including pain, depression, and addiction. However, stimulation or blockade of any one opioid receptor type often leads to on-target adverse effects that limit the clinical utility of a selective opioid agonist or antagonist. Literature precedent suggests that the opioid receptors do not act in isolation and that interactions among the opioid receptors and between the opioid receptors and other proteins may produce clinically useful targets...
April 20, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29674125/deciphering-the-role-of-dimer-interface-in-intrinsic-dynamics-and-allosteric-pathways-underlying-the-functional-transformation-of-dnmt3a
#6
Zhongjie Liang, Junchi Hu, Wenying Yan, Hualiang Jiang, Guang Hu, Cheng Luo
BACKGROUND: DNMT3A, as de novo DNA methyltransferase, is essential for regulating gene expression through cellular development and differentiation. The functions of DNMT3A rely on its oligomeric states and allosteric regulations between its catalytic domain and binding partners. Despite recent resolution of autoinhibitory and active DNMT3A/3L crystal structures, the mechanism of their functional motions and interdomain allostery in regulating the activity remains to be established. METHODS: The hybrid approach, comprising Elastic Network Models coupled with information theory, Protein Structure Network, and sequence evolution analysis was employed to investigate intrinsic dynamics and allosteric properties of DNMT3A resolved in autoinhibitory and active states...
April 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29673544/no-effect-of-creatine-monohydrate-supplementation-on-inflammatory-and-cartilage-degradation-biomarkers-in-individuals-with-knee-osteoarthritis
#7
Stephen M Cornish, Jason D Peeler
The study purpose was to evaluate the effectiveness of creatine monohydrate supplementation (20 grams/day for 1 week and then 5 grams/day for 11 weeks) on inflammation (C-reactive protein, interleukin-1β, interleukin-6, s100 A8/A9, and tumor necrosis factor-α) and cartilage degradation (serum cartilage oligomeric matrix protein) in patients with knee osteoarthritis. We hypothesized that supplementing with creatine monohydrate for 12 weeks would lower biomarkers of inflammation and cartilage degradation in patients with knee osteoarthritis when compared to placebo...
March 2018: Nutrition Research
https://www.readbyqxmd.com/read/29673150/immunohistochemical-evidence-from-app-transgenic-mice-for-glutaminyl-cyclase-as-drug-target-to-diminish-pe-abeta-formation
#8
Maike Hartlage-Rübsamen, Alexandra Bluhm, Anke Piechotta, Miriam Linnert, Jens-Ulrich Rahfeld, Hans-Ulrich Demuth, Inge Lues, Peer-Hendrik Kuhn, Stefan F Lichtenthaler, Steffen Roßner, Corinna Höfling
Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer’s disease (AD). In recent years, a substantial heterogeneity of Abeta peptides with distinct biophysical and cell biological properties has been demonstrated. Among these, a particularly neurotoxic and disease-specific Abeta variant is N-terminally truncated and modified to pyroglutamate (pE-Abeta). Cell biological and animal experimental studies imply the catalysis of this modification by the enzyme glutaminyl cyclase (QC)...
April 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29671171/new-use-for-cetsa-monitoring-innate-immune-receptor-stability-via-post-translational-modification-by-ogt
#9
Walter R Drake, Ching-Wen Hou, Natasha E Zachara, Catherine Leimkuhler Grimes
O-GlcNAcylation is a dynamic and functionally diverse post-translational modification shown to affect thousands of proteins, including the innate immune receptor nucleotide-binding oligomerization domain-containing protein 2 (Nod2). Mutations of Nod2 (R702W, G908R and 1007 fs) are associated with Crohn's disease and have lower stabilities compared to wild type. Cycloheximide (CHX)-chase half-life assays have been used to show that O-GlcNAcylation increases the stability and response of both wild type and Crohn's variant Nod2, R702W...
April 18, 2018: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/29669811/linker-engineering-in-anti-tag-72-antibody-fragments-optimizes-biophysical-properties-serum-half-life-and-high-specificity-tumor-imaging
#10
Nicholas E Long, Brandon J Sullivan, Haiming Ding, Stephanie R Doll, Michael A Ryan, Charles L Hitchcock, Edward W Martin, Krishan Kumar, Michael F Tweedle, Thomas J Magliery
Antibody (Ab) fragments have great clinical potential as cancer therapeutics and diagnostics. Their small size allows for fast clearance from blood, low immunoreactivity, better tumor penetration, and simpler engineering and production. The smallest fragment derived from a full-length IgG that retains binding to its antigen, the single-chain variable fragment (scFV), is engineered by fusing the variable light and variable heavy domains with a peptide linker. Along with switching the domain orientation, altering the length and amino acid sequence of the linker can significantly affect scFV binding, stability, quaternary structure, and other biophysical properties...
April 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29669320/camkii-potentiates-store-operated-ca2-entry-through-enhancing-stim1-aggregation-and-interaction-with-orai1
#11
Shu Li, Jingyi Xue, Zhipeng Sun, Tiantian Liu, Lane Zhang, Limin Wang, Hongjie You, Zheng Fan, Yuanyuan Zheng, Dali Luo
BACKGROUND/AIMS: Upon Ca2+ store depletion, stromal interaction molecule 1 (STIM1) oligomerizes, redistributes near plasmalemma to interact with Ca2+ selective channel-forming subunit (Orai1) and initiates store-operated Ca2+ entry (SOCE). Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a regulator of SOCE, but how CaMKII regulates SOCE remains obscure. METHODS: Using Fura2, confocal microscopy, co-immunoprecipitation, specific blocker and overexpression/knockdown approaches, we evaluated STIM1 aggregation and its interaction with Orai1, and SOCE upon Ca2+ store depletion in thapsigargin (TG) treated HEK293 and HeLa cells...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29668350/the-tomosyn-homolog-sro7-is-a-direct-effector-of-the-rab-gtpase-sec4-in-post-golgi-vesicle-tethering
#12
Guendalina Rossi, Kelly Watson, Wade Kennedy, Patrick Brennwald
The tomosyn/Sro7 family is thought to play an important role in cell surface trafficking both as an effector of Rab family GTPases and as a regulator of plasma membrane SNARE function. Recent work has determined the binding site of GTP-bound Sec4 on Sro7. Here we examine the effect of mutations in Sro7 that block Sec4 binding to determine the role of this interaction in Sro7 function. Using an in vitro vesicle:vesicle tethering assay, we find that most of Sro7's ability to tether vesicles is blocked by mutations that disrupt binding to Sec4-GTP...
April 18, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29667617/combination-of-stromal-vascular-fraction-and-ad-comp-ang1-gene-therapy-improves-long-term-therapeutic-efficacy-for-diabetes-induced-erectile-dysfunction
#13
Guo-Nan Yin, Lin Wang, Xiang-Nan Lin, Lei Shi, Zhen-Lin Gao, Feng-Chan Han, Ping Li, Yin-Chuan Jin, Jun-Kyu Suh, Ji-Kan Ryu, Xiong Wang, Hai-Rong Jin
Men with diabetic erectile dysfunction (ED) respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. Stromal vascular fraction (SVF) and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 (Ad-COMP-Ang1) gene are known to play critical roles in penile erection. We previously reported that SVF and Ad-COMP-Ang1 have only a short-term effect in restoring erectile function. Further improvements to ED therapy are needed for long-lasting effects...
April 17, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29666700/oil-palm-phenolics-inhibit-the-in-vitro-aggregation-of-%C3%AE-amyloid-peptide-into-oligomeric-complexes
#14
Robert P Weinberg, Vera V Koledova, Hyeari Shin, Jennifer H Park, Yew Ai Tan, Anthony J Sinskey, Ravigadevi Sambanthamurthi, ChoKyun Rha
Alzheimer's disease is a severe neurodegenerative disease characterized by the aggregation of amyloid- β peptide (A β ) into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of A β 42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that A β 42 aggregation is inhibited in vitro by oil palm phenolics (OPP), an aqueous extract from the oil palm tree (Elaeis guineensis) ...
2018: International Journal of Alzheimer's Disease
https://www.readbyqxmd.com/read/29666631/structural-basis-for-ph-dependent-oligomerization-of-dihydropyrimidinase-from-pseudomonas-aeruginosa-pao1
#15
Jen-Hao Cheng, Chien-Chih Huang, Yen-Hua Huang, Cheng-Yang Huang
Dihydropyrimidinase, a dimetalloenzyme containing a carboxylated lysine within the active site, is a member of the cyclic amidohydrolase family, which also includes allantoinase, dihydroorotase, hydantoinase, and imidase. Unlike all known dihydropyrimidinases, which are tetrameric, pseudomonal dihydropyrimidinase forms a dimer at neutral pH. In this paper, we report the crystal structure of P. aeruginosa dihydropyrimidinase at pH 5.9 (PDB entry 5YKD). The crystals of P. aeruginosa dihydropyrimidinase belonged to space group C 2221 with cell dimensions of a  = 108...
2018: Bioinorganic Chemistry and Applications
https://www.readbyqxmd.com/read/29666477/single-cell-analysis-of-pyroptosis-dynamics-reveals-conserved-gsdmd-mediated-subcellular-events-that-precede-plasma-membrane-rupture
#16
Nathalia M de Vasconcelos, Nina Van Opdenbosch, Hanne Van Gorp, Eef Parthoens, Mohamed Lamkanfi
Pyroptosis is rapidly emerging as a mechanism of anti-microbial host defense, and of extracellular release of the inflammasome-dependent cytokines interleukin (IL)-1β and IL-18, which contributes to autoinflammatory pathology. Caspases 1, 4, 5 and 11 trigger this regulated form of necrosis by cleaving the pyroptosis effector gasdermin D (GSDMD), causing its pore-forming amino-terminal domain to oligomerize and perforate the plasma membrane. However, the subcellular events that precede pyroptotic cell lysis are ill defined...
April 17, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29666248/study-of-protein-folding-under-native-conditions-by-rapidly-switching-the-hydrostatic-pressure-inside-an-nmr-sample-cell
#17
Cyril Charlier, T Reid Alderson, Joseph M Courtney, Jinfa Ying, Philip Anfinrud, Adriaan Bax
In general, small proteins rapidly fold on the timescale of milliseconds or less. For proteins with a substantial volume difference between the folded and unfolded states, their thermodynamic equilibrium can be altered by varying the hydrostatic pressure. Using a pressure-sensitized mutant of ubiquitin, we demonstrate that rapidly switching the pressure within an NMR sample cell enables study of the unfolded protein under native conditions and, vice versa, study of the native protein under denaturing conditions...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666246/large-sod1-aggregates-unlike-trimeric-sod1-do-not-impact-cell-viability-in-a-model-of-amyotrophic-lateral-sclerosis
#18
Cheng Zhu, Matthew V Beck, Jack D Griffith, Mohanish Deshmukh, Nikolay V Dokholyan
Aberrant accumulation of misfolded Cu, Zn superoxide dismutase (SOD1) is a hallmark of SOD1-associated amyotrophic lateral sclerosis (ALS), an invariably fatal neurodegenerative disease. While recent discovery of nonnative trimeric SOD1-associated neurotoxicity has suggested a potential pathway for motor neuron impairment, it is yet unknown whether large, insoluble aggregates are cytotoxic. Here we designed SOD1 mutations that specifically stabilize either the fibrillar form or the trimeric state of SOD1. The designed mutants display elevated populations of fibrils or trimers correspondingly, as demonstrated by gel filtration chromatography and electron microscopy...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29665254/designing-liquid-crystalline-oligomers-to-exhibit-twist-bend-modulated-nematic-phases
#19
REVIEW
Richard J Mandle
Arguably the most active area in liquid crystal research presently, the twist-bend modulated nematic phase (TB) exhibits a nanoscale helical structure and therefore exhibits bulk chirality despite being formed of typically achiral materials. After a short introduction we address the structure-property relationship that exists for this unique mesophase before introducing recent advances in strategies employed to prepare oligomeric materials that exhibit this state of matter. These methods afford fine control over the molecular substructure and potentially over the nanostructure of the exhibited mesophases...
April 17, 2018: Chemical Record: An Official Publication of the Chemical Society of Japan ... [et Al.]
https://www.readbyqxmd.com/read/29663486/calmodulin-antagonist-enhances-dr5-mediated-apoptotic-signaling-in-tra-8-resistant-triple-negative-breast-cancer-cells
#20
Romone M Fancy, Harrison Kim, Tiara Napier, Donald J Buchsbaum, Kurt R Zinn, Yuhua Song
Patients with triple negative breast cancer (TNBC) have no successful "targeted" treatment modality, which represents a priority for novel therapy strategies. Upregulated death receptor 5 (DR5) expression levels in breast cancer cells compared to normal cells enable TRA-8, a DR5 specific agonistic antibody, to specifically target malignant cells for apoptosis without inducing normal hepatocyte apoptosis. Drug resistance is a common obstacle in TRAIL-based therapy for TNBC. Calmodulin (CaM) is overexpressed in breast cancer...
April 16, 2018: Journal of Cellular Biochemistry
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