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https://www.readbyqxmd.com/read/29218636/incorporation-of-second-coordination-sphere-d-amino-acids-alters-cd-ii-geometries-in-designed-thiolate-rich-proteins
#1
Leela Ruckthong, Aniruddha Deb, Lars Hemmingsen, James E Penner-Hahn, Vincent L Pecoraro
We use a de Novo protein design strategy to demonstrate that the second coordination sphere of a metal site plays a key role in controlling coordination geometries of Cd(II)-tris-thiolate complexes. Specifically, we show that alteration of chirality within the core hydrophobic packing region of a three-stranded coiled coil (3SCC) can control the coordination number of Cd(II) by limiting steric encumbrance to the metal center. Within a specific class of 3SCCs [Ac-G-(LKALEEK) n -G-NH2], where n = 4 is TRI and n = 5 is GRAND, one L-Leu may be substituted by L-Cys to generate a planar tris-thiolate array capable of metal binding...
December 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29217616/interactome-mapping-uncovers-a-general-role-for-numb-in-protein-kinase-regulation
#2
Ran Wei, Tomonori Kaneko, Xuguang Liu, Huadong Liu, Lei Li, Courtney Voss, Eric Liu, Ningning He, Shawn S C Li
Cellular functions are frequently regulated by protein-protein interactions involving the binding of a modular domain in one protein to a specific peptide sequence in another.  This mechanism may be explored to identify binding partners for proteins harboring a peptide-recognition domain. Here we report a proteomic strategy combining peptide and protein microarray screening with biochemical and cellular assays to identify modular domain-mediated protein-protein interactions in a systematic manner. We applied this strategy to Numb, a multi-functional protein containing a phosphotyrosine-binding (PTB) domain...
December 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29216473/the-natural-sesquiterpene-lactones-arglabin-grosheimin-agracin-parthenolide-and-estafiatin-inhibit-t-cell-receptor-tcr-activation
#3
Igor A Schepetkin, Liliya N Kirpotina, Pete T Mitchell, Аnarkul S Kishkentaeva, Zhanar R Shaimerdenova, Gayane A Atazhanova, Sergazy M Adekenov, Mark T Quinn
Inhibition of the T cell receptor (TCR) pathway represents an effective strategy for the treatment of T cell-mediated inflammatory and autoimmune diseases. To identify natural compounds that could inhibit inflammatory T cell responses, we screened 13 sesquiterpene lactones, including achillin, arglabin, argolide, argracin, 3β-hydroxyarhalin, artesin, artemisinin, estafiatin, grosheimin, grossmisin, leucomisine, parthenolide, and taurine, for their ability to modulate activation-induced Ca2+ mobilization in Jurkat T cells...
December 4, 2017: Phytochemistry
https://www.readbyqxmd.com/read/29215605/cone-snails-a-big-store-of-conotoxins-for-novel-drug-discovery
#4
REVIEW
Bingmiao Gao, Chao Peng, Jiaan Yang, Yunhai Yi, Junqing Zhang, Qiong Shi
Marine drugs have developed rapidly in recent decades. Cone snails, a group of more than 700 species, have always been one of the focuses for new drug discovery. These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or conopeptides. These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and affinity to ion channels, receptors, and transporters in the nervous systems of target prey and humans...
December 7, 2017: Toxins
https://www.readbyqxmd.com/read/29205458/multi-disciplinary-management-of-refractory-insulinomas
#5
Emily Brown, Daniel Watkin, Jonathan Evans, Vincent Yip, Daniel J Cuthbertson
Insulinomas are predominantly benign (~90%), pancreatic neuroendocrine tumours characterised by hyperinsulinaemic hypoglycaemia. They usually present as a small (<2cm), well demarcated, solitary nodule that can arise in any part of the organ. Treatment of sporadic insulinomas is generally aimed at curative surgical resection with special consideration in genetic syndromes. Patients with significant hypoglycaemia can pose a difficult management challenge. In isolated cases where the patient is not medically fit for surgery or with metastatic spread, other treatment options are employed...
December 4, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/29203198/phylogeny-and-expression-patterns-of-two-apolipoprotein-e-genes-in-the-flatfish-senegalese-sole
#6
Javier Roman-Padilla, Ana Rodríguez-Rúa, Carlos Carballo, Manuel Manchado, Ismael Hachero-Cruzado
The apolipoprotein E (ApoE) is a key component of several lipoproteins involved in lipid homeostasis. In this study, two cDNA sequences encoding ApoE (referred to as apoEa and apoEb) were characterized in the flatfish Solea senegalensis. The predicted peptides contained conserved structural blocks related with their capacity for lipid binding and lipoprotein receptor interaction. At genomic level, both genes contained five exons and four introns and they were organized into two tandem arrays with apoA-IV gene copies...
December 1, 2017: Gene
https://www.readbyqxmd.com/read/29194460/dynamical-system-modeling-to-simulate-donor-t-cell-response-to-whole-exome-sequencing-derived-recipient-peptides-understanding-randomness-in-alloreactivity-incidence-following-stem-cell-transplantation
#7
Vishal Koparde, Badar Abdul Razzaq, Tara Suntum, Roy Sabo, Allison Scalora, Myrna Serrano, Max Jameson-Lee, Charles Hall, David Kobulnicky, Nihar Sheth, Juliana Feltz, Daniel Contaifer, Dayanjan Wijesinghe, Jason Reed, Catherine Roberts, Rehan Qayyum, Gregory Buck, Michael Neale, Amir Toor
Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA) and graft versus host disease (GVHD) pathophysiology in stem cell transplant (SCT) donor-recipient pairs (DRP) is not established. In order to elucidate this relationship, whole exome sequencing (WES) was performed on 27 HLA matched related (MRD), & 50 unrelated donors (URD), to identify nonsynonymous single nucleotide polymorphisms (SNPs). An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p<0...
2017: PloS One
https://www.readbyqxmd.com/read/29176623/microneedle-array-patches-loaded-with-dual-mineralized-protein-peptide-particles-for-type-2-diabetes-therapy
#8
Wei Chen, Rui Tian, Can Xu, Bryant C Yung, Guohao Wang, Yijing Liu, Qianqian Ni, Fuwu Zhang, Zijian Zhou, Jingjing Wang, Gang Niu, Ying Ma, Liwu Fu, Xiaoyuan Chen
The delivery of therapeutic peptides for diabetes therapy is compromised by short half-lives of drugs with the consequent need for multiple daily injections that reduce patient compliance and increase treatment cost. In this study, we demonstrate a smart exendin-4 (Ex4) delivery device based on microneedle (MN)-array patches integrated with dual mineralized particles separately containing Ex4 and glucose oxidase (GOx). The dual mineralized particle-based system can specifically release Ex4 while immobilizing GOx as a result of the differential response to the microenvironment induced by biological stimuli...
November 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29172549/proteomic-characterization-of-dermal-interstitial-fluid-extracted-using-a-novel-microneedle-assisted-technique
#9
Bao Quoc Tran, Philip R Miller, Robert M Taylor, Gabrielle Boyd, Phillip M Mach, C Nicole Rosenzweig, Justin T Baca, Ronen Polsky, Trevor Glaros
As commercial wearable fitness devices have gained commercial acceptance, interest in-real time monitoring of an individual's physiological status using non-invasive techniques has grown. Microneedles have been proposed as a minimally invasive technique for sampling the dermal interstitial fluid (ISF) for clinical monitoring and diagnosis, but little is known about its composition. In this study, dermal ISF was collected using novel microneedle array from three healthy human donors and compared to matching serum and plasma samples...
November 24, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29165244/the-aaa-atpase-vps4-binds-escrt-iii-substrates-through-a-repeating-array-of-dipeptide-binding-pockets
#10
Han Han, Nicole Monroe, Wesley I Sundquist, Peter S Shen, Christopher P Hill
The hexameric AAA ATPase Vps4 drives membrane fission by remodeling and disassembling ESCRT-III filaments. Building upon our earlier 4.3 Å resolution cryo-EM structure (Monroe, Han et al. 2017), we now report a 3.2 Å structure of Vps4 bound to an ESCRT-III peptide substrate. The new structure reveals that the peptide approximates a b-strand conformation whose helical symmetry matches that of the five Vps4 subunits it contacts directly. Adjacent Vps4 subunits make equivalent interactions with successive substrate dipeptides through two distinct classes of side chain binding pockets formed primarily by Vps4 pore loop 1...
November 22, 2017: ELife
https://www.readbyqxmd.com/read/29157277/a-validated-antibody-panel-for-the-characterization-of-tau-post-translational-modifications
#11
Ebru Ercan, Sameh Eid, Christian Weber, Alexandra Kowalski, Maria Bichmann, Annika Behrendt, Frank Matthes, Sybille Krauss, Peter Reinhardt, Simone Fulle, Dagmar E Ehrnhoefer
BACKGROUND: Tau is a microtubule-binding protein, which is subject to various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Aberrant PTMs such as hyperphosphorylation result in tau aggregation and the formation of neurofibrillary tangles, which are a hallmark of Alzheimer's disease (AD). In order to study the importance of PTMs on tau function, antibodies raised against specific modification sites are widely used...
November 21, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29156741/screening-epitopes-on-systemic-lupus-erythematosus-autoantigens-with-a-peptide-array
#12
Lin Wang, Chenjun Hao, Yongqiu Deng, Yanbo Liu, Shiliang Hu, Yangang Peng, Manna He, Jinhu Fu, Ming Liu, Jia Chen, Xiaoming Chen
Systemic lupus erythematosus (SLE) is a common autoimmune disease. Many autoantibodies are closely associated with SLE. However, the specific epitopes recognized and bound by these autoantibodies are still unclear. This study screened the binding epitopes of SLE-related autoantibodies using a high-throughput screening method. Epitope prediction on 12 SLE-related autoantigens was performed using the Immune Epitope Database and Analysis Resource (IEDB) software. The predicted epitopes were synthesized into peptides and developed into a peptide array...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155769/a-simple-approach-to-induce-experimental-autoimmune-neuritis-in-c57bl-6-mice-for-functional-and-neuropathological-assessments
#13
David G Gonsalvez, Jessica L Fletcher, Sang Won Yoo, Rhiannon J Wood, Simon S Murray, Junhua Xiao
Experimental autoimmune neuritis (EAN) is a well-appreciated experimental model of autoimmune peripheral demyelinating diseases. EAN disease is induced by immunizing mice with neurogenic peptides to direct an inflammatory attack toward components of the peripheral nervous system (PNS). Recent advances have enabled the induction of EAN in the relatively resistant C57BL/6 mouse line using myelin protein zero (P0)106-125 or P0180-199 peptides delivered in adjuvant combined with the injection of pertussis toxin...
November 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29151691/parallel-mrna-proteomics-and-mirna-expression-analysis-in-cell-line-models-of-the-intestine
#14
Finbarr O'Sullivan, Joanne Keenan, Sinead Aherne, Fiona O'Neill, Colin Clarke, Michael Henry, Paula Meleady, Laura Breen, Niall Barron, Martin Clynes, Karina Horgan, Padraig Doolan, Richard Murphy
AIM: To identify miRNA-regulated proteins differentially expressed between Caco2 and HT-29: two principal cell line models of the intestine. METHODS: Exponentially growing Caco-2 and HT-29 cells were harvested and prepared for mRNA, miRNA and proteomic profiling. mRNA microarray profiling analysis was carried out using the Affymetrix GeneChip Human Gene 1.0 ST array. miRNA microarray profiling analysis was carried out using the Affymetrix Genechip miRNA 3.0 array...
November 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29150077/unique-arginine-array-improves-cytosolic-localization-of-hydrocarbon-stapled-peptides
#15
Kim Quach, Jonathan LaRochelle, Xiao-Han Li, Elizabeth Rhoades, Alanna Schepartz
We have previously reported that miniature proteins containing a distinct array of 5 arginine residues on a folded α-helix - a penta-arg motif - traffic with high efficiency from endosomes into the cytosol and nucleus of mammalian cells. Here we evaluate whether a penta-arg motif can improve the intracellular trafficking of an otherwise impermeant hydrocarbon-stapled peptide, SAH-p53-4(Rho). We prepared a panel of SAH-p53-4(Rho) variants containing penta-arg sequences with different spacings and axial arrangement and evaluated their overall uptake (as judged by flow cytometry) and their intracellular access (as determined by fluorescence correlation spectroscopy, FCS)...
November 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29141920/parathyroid-hormone-related-protein-modulates-mice-mesangial-cells-inflammation-and-blunts-apoptosis-by-enhancing-cox-2-expression
#16
Mazène Hochane, Denis Raison, Catherine Coquard, Claire Béraud, Audrey Bethry, Sabrina Danilin, Thierry Massfelder, Mariette Barthelmebs
Mesangial cell (MC) injury is a prominent feature of glomerulonephritis. Activated MC secretes inflammatory mediators which induce cell apoptosis. Parathyroid hormone-related peptide (PTHrP) is a locally active cytokine that enhances cell survival and is upregulated by pro-inflammatory factors in many cell types. The aim of this study was to analyze the regulation of PTHrP expression by inflammatory cytokines, and to evaluate whether PTHrP itself acts as a pro-inflammatory and/or survival factor on male murine MC in primary culture...
November 15, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29139514/differential-array-sensing-for-cancer-cell-classification-and-novelty-detection
#17
Alexandra M Gade, Margaret K Meadows, Andrew D Ellington, Eric V Anslyn
A series of semi-specific peptides reported in the literature to bind various epitopes on cell surfaces were used in a differential sensing array to pattern cell line identity. The peptides were conjugated to thiazole orange to act as both a fluorescence reporter and a DNA intercalator. Fluorescence data for the peptides exposed to cells, with and without exogenous double stranded DNA (dsDNA), led to chemometric fingerprints for eight cancer cell lines. In contrast to the use of structures meant to act in completely non-specific ways, the use of a limited level of specificity generated linear discriminant score plots with high dimensionality, i...
November 15, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29135227/peptide-arrays-development-and-application
#18
Lindsey Szymczak, Hsin-Yu Kuo, Milan Mrksich
Peptide arrays are an exciting and rapidly growing technology with a broad range of applications in the basic and applied life sciences. Peptide arrays have been under development for approximately twenty-five years, and commercial versions have been available for the past decade. The arrays typically comprise hundreds to thousands of distinct peptide sequences, and have proven important for determining substrate specificities of enzymes, profiling antibodies and mapping epitopes, studying ligand-receptor interactions and identifying ligands that mediate cell adhesion...
November 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29133874/distinct-roles-of-nmb-and-grp-in-itch-transmission
#19
Li Wan, Hua Jin, Xian-Yu Liu, Joseph Jeffry, Devin M Barry, Kai-Feng Shen, Jia-Hang Peng, Xue-Ting Liu, Jin-Hua Jin, Yu Sun, Ray Kim, Qing-Tao Meng, Ping Mo, Jun Yin, Ailin Tao, Rita Bardoni, Zhou-Feng Chen
A key question in our understanding of itch coding mechanisms is whether itch is relayed by dedicated molecular and neuronal pathways. Previous studies suggested that gastrin-releasing peptide (GRP) is an itch-specific neurotransmitter. Neuromedin B (NMB) is a mammalian member of the bombesin family of peptides closely related to GRP, but its role in itch is unclear. Here, we show that itch deficits in mice lacking NMB or GRP are non-redundant and Nmb/Grp double KO (DKO) mice displayed additive deficits. Furthermore, both Nmb/Grp and Nmbr/Grpr DKO mice responded normally to a wide array of noxious stimuli...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133117/application-of-mixed-peptide-arrays-to-study-combinatorial-readout-of-chromatin-modifications
#20
Rebekka Mauser, Goran Kungulovski, David Meral, Daniel Maisch, Albert Jeltsch
The N-terminal tails of histone proteins are massively decorated with post-translational modifications (PTMs), which play important roles in the regulation of gene expression. Several highly conserved chromatin interacting proteins can bind to histone modifications in a sequence and modification specific manner employing specific reading domains. These proteins often contain several reading domains, which can cooperate in the readout of different PTMs. To gain a better insight into the combinatorial readout of PTMs, we developed a method to study the binding of double reading domains to mixed peptide arrays containing two different peptides in each spot...
November 10, 2017: Biochimie
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