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Intrinsically disordered protein

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https://www.readbyqxmd.com/read/28935930/characterization-of-soft-amyloid-cores-in-human-prion-like-proteins
#1
Cristina Batlle, Natalia Sanchez de Groot, Valentin Iglesias, Susanna Navarro, Salvador Ventura
Prion-like behaviour is attracting much attention due to the growing evidences that amyloid-like self-assembly may reach beyond neurodegeneration and be a conserved functional mechanism. The best characterized functional prions correspond to a subset of yeast proteins involved in translation or transcription. Their conformational promiscuity is encoded in Prion Forming Domains (PFDs), usually long and intrinsically disordered protein segments of low complexity. The compositional bias of these regions seems to be important for the transition between soluble and amyloid-like states...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935721/the-spliceosomal-proteins-ppih-and-prpf4-exhibit-bipartite-binding
#2
Caroline Rajiv, S RaElle Jackson, Simon Cocklin, Elan Z Eisenmesser, Tara Davis
Pre-mRNA splicing is a dynamic, multi-step process that is catalyzed by the RNA: protein complex called the spliceosome. The spliceosome contains a core set of RNAs and proteins that are conserved in all organisms that perform splicing. In higher organisms, PPIH directly interacts with the core protein PRPF4 and both integrate into the pre-catalytic spliceosome as part of the tri-snRNP sub-complex. As a first step to understand the protein interactions that dictate PPIH and PRPF4 function, we expressed and purified soluble forms of each protein and formed a complex between them...
September 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28934129/a-comprehensive-survey-of-the-roles-of-highly-disordered-proteins-in-type-2-diabetes
#3
Zhihua Du, Vladimir N Uversky
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with hyperglycemia (high blood sugar) related to either insulin resistance or insufficient insulin production. Among the various molecular events and players implicated in the manifestation and development of diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database has information on 34 human proteins experimentally shown to be related to the T2DM pathogenesis...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28931924/chimeric-14-3-3-proteins-for-unraveling-interactions-with-intrinsically-disordered-partners
#4
Nikolai N Sluchanko, Kristina V Tugaeva, Sandra J Greive, Alfred A Antson
In eukaryotes, several "hub" proteins integrate signals from different interacting partners that bind through intrinsically disordered regions. The 14-3-3 protein hub, which plays wide-ranging roles in cellular processes, has been linked to numerous human disorders and is a promising target for therapeutic intervention. Partner proteins usually bind via insertion of a phosphopeptide into an amphipathic groove of 14-3-3. Structural plasticity in the groove generates promiscuity allowing accommodation of hundreds of different partners...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928907/adipose-derived-stromal-cell-in-regenerative-medicine-a-review
#5
REVIEW
Reza Tabatabaei Qomi, Mohsen Sheykhhasan
The application of appropriate cell origin for utilizing in regenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several stromal cells have been employed as treat option for regenerative medicine. For example, human bone marrow-derived stromal cells and adipose-derived stromal cells (ADSCs) are used in cell-based therapy. Data relating to the stem cell therapy and processes associated with ADSC has developed remarkably in the past 10 years...
August 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28928219/o2-sensing-associated-glycosylation-exposes-the-f-box-combining-site-of-the-dictyostelium-skp1-subunit-in-e3-ubiquitin-ligases
#6
M Osman Sheikh, David Thieker, Gordon Chalmers, Christopher M Schafer, Mayumi Ishihara, Parastoo Azadi, Robert J Woods, John N Glushka, Brad Bendiak, James H Prestegard, Christopher M West
Skp1 is a conserved protein linking cullin-1 to F-box proteins in SCF (Skp1-Cullin1-F-box) E3 ubiquitin ligases, which modify protein substrates with polyubiquitin chains that typically target them for 26S proteasome-mediated degradation. In Dictyostelium (a social amoeba), Toxoplasma gondii (the agent for human toxoplasmosis), and other protists, Skp1 is regulated by a unique pentasaccharide attached to hydroxylated Pro-143 within its C-terminal F-box binding domain. Prolyl hydroxylation of Skp1 contributes to O2-dependent Dictyostelium development, but full glycosylation at that position is required for optimal O2 sensing...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28928136/endothelial-epas1-deficiency-is-sufficient-to-promote-parietal-epithelial-cell-activation-and-fsgs-in-experimental-hypertension
#7
Yosu Luque, Olivia Lenoir, Philippe Bonnin, Lise Hardy, Anna Chipont, Sandrine Placier, Sophie Vandermeersch, Yi-Chun Xu-Dubois, Blaise Robin, Hélène Lazareth, Michèle Souyri, Léa Guyonnet, Véronique Baudrie, Eric Camerer, Eric Rondeau, Laurent Mesnard, Pierre-Louis Tharaux
FSGS, the most common primary glomerular disorder causing ESRD, is a complex disease that is only partially understood. Progressive sclerosis is a hallmark of FSGS, and genetic tracing studies have shown that parietal epithelial cells participate in the formation of sclerotic lesions. The loss of podocytes triggers a focal activation of parietal epithelial cells, which subsequently form cellular adhesions with the capillary tuft. However, in the absence of intrinsic podocyte alterations, the origin of the pathogenic signal that triggers parietal epithelial cell recruitment remains elusive...
September 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28928079/polyglutamine-expansion-diseases-more-than-simple-repeats
#8
Alexandra Silva, Ana Viana de Almeida, Sandra Macedo-Ribeiro
Polyglutamine (polyQ) repeat-containing proteins are widespread in the human proteome but only nine of them are associated with highly incapacitating neurodegenerative disorders. The genetic expansion of the polyQ tract in disease-related proteins triggers a series of events resulting in neurodegeneration. The polyQ tract plays the leading role in the aggregation mechanism, but other elements modulate the aggregation propensity in the context of the full-length proteins, as implied by variations in the length of the polyQ tract required to trigger the onset of a given polyQ disease...
September 16, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28926706/structural-and-kinetic-characterization-of-the-intrinsically-disordered-protein-sev-ntail-through-enhanced-sampling-simulations
#9
Mattia Bernetti, Matteo Masetti, Fabio Pietrucci, Martin Blackledge, Malene Ringkjøbing Jensen, Maurizio Recanatini, Luca Mollica, Andrea Cavalli
Intrinsically disordered proteins (IDPs) are emerging as an important class of the proteome. Being able to interact with different molecular targets, they participate in many physiological and pathological activities. However, due to their intrinsically heterogeneous nature, determining the equilibrium properties of IDPs is still a challenge for biophysics. Herein, we applied state-of-the-art enhanced sampling methods to Sev NTAIL, a test case of IDPs, and constructed a bin-based kinetic model to unveil the underlying kinetics...
September 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28924037/intrinsically-disordered-sequences-enable-modulation-of-protein-phase-separation-through-distributed-tyrosine-motifs
#10
Yuan Lin, Simon L Currie, Michael Keith Rosen
Liquid-liquid phase separation (LLPS) is thought to contribute to establishment of many biomolecular condensates, eukaryotic cell structures that concentrate diverse macromolecules but lack a bounding membrane. RNA granules control RNA metabolism and comprise a large class of condensates that are enriched in RNA-binding proteins and RNA molecules. Many RNA granule proteins are composed of both modular domains and intrinsically disordered regions (IDRs) having low amino acid sequence complexity. Phase separation of these molecules likely plays an important role in the generation and stability of RNA granules...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28924012/inhibition-of-il-1%C3%AE-signaling-normalizes-nmda-dependent-neurotransmission-and-reduces-seizure-susceptibility-in-a-mouse-model-of-creutzfeldt-jakob-disease
#11
Ilaria Bertani, Valentina Iori, Massimo Trusel, Mattia Maroso, Claudia Foray, Susanna Mantovani, Raffaella Tonini, Annamaria Vezzani, Roberto Chiesa
Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disorder caused by prion protein (PrP) misfolding, clinically recognized by cognitive and motor deficits, electroencephalographic (EEG) abnormalities and seizures. Its neurophysiological bases are not known. To assess the potential involvement of N-methyl-D-aspartate receptor (NMDAR) dysfunction, we analyzed NMDA-dependent synaptic plasticity in hippocampal slices from Tg(CJD) mice, which model a genetic form of CJD. Because PrP depletion may result in functional upregulation of NMDARs, we also analyzed PrP knockout (KO) mice...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28920762/measuring-dynamics-of-eukaryotic-transcription-initiation-challenges-insights-and-opportunities
#12
Zhengjian Zhang, Robert Tjian
Transcription of protein-encoding genes in eukaryotic cells is a dynamically coordinated process. Many of the key transcription regulators contain functionally essential intrinsically disordered regions (IDRs), the dynamic nature of which creates extra challenges to traditional biochemical analyses. Recent advances in single-molecule fluorescence imaging technology have enabled direct visualization of these rapid, complex and dynamic molecular interactions in real time.
September 18, 2017: Transcription
https://www.readbyqxmd.com/read/28918091/opposed-effects-of-dityrosine-formation-in-soluble-and-aggregated-%C3%AE-synuclein-on-fibril-growth
#13
Michael M Wördehoff, Hamed Shaykhalishahi, Luca Groß, Lothar Gremer, Matthias Stoldt, Alexander K Buell, Dieter Willbold, Wolfgang Hoyer
Parkinson's disease (PD) is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY)-crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from PD patients. Here we report that α-syn is highly susceptible to UV-induced DiY formation...
September 13, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28917842/multi-scale-simulations-of-biological-systems-using-the-opep-coarse-grained-model
#14
Fabio Sterpone, Sébastien Doutreligne, Thanh Thuy Tran, Simone Melchionna, Marc Baaden, Phuong H Nguyen, Philippe Derreumaux
Biomolecules are complex machines that are optimized by evolution to properly fulfill or contribute to a variety of biochemical tasks in the cellular environment. Computer simulations based on quantum mechanics and atomistic force fields have been proven to be a powerful microscope for obtaining valuable insights into many biological, physical, and chemical processes. Many interesting phenomena involve, however, a time scale and a number of degrees of freedom, notably if crowding is considered, that cannot be explored at an atomistic resolution...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28917050/preparation-of-selenocysteine-containing-forms-of-human-selenok-and-selenos
#15
Zhengqi Zhang, Jun Liu, Sharon Rozovsky
Selenoprotein K (SELENOK) and Selenoprotein S (SELENOS) are the members of the endoplasmic-reticulum-associated degradation (ERAD) complex, which is responsible for translocating misfolded proteins from the endoplasmic reticulum (ER) to the cytosol for degradation. Besides its involvement in the ERAD, SELENOK was shown to bind and stabilize the palmitoyl transferase DHHC6, and thus contributes to palmitoylation. SELENOK and SELENOS reside in the ER membrane by the way of a single transmembrane helix. Both contain an intrinsically disordered region with a selenocysteine (Sec) located one or two residues away from the C-terminus...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28914483/the-thermodynamic-basis-of-the-fuzzy-interaction-of-an-intrinsically-disordered-protein
#16
San Hadži, Andrej Mernik, Črtomir Podlipnik, Remy Loris, Jurij Lah
Many intrinsically disordered proteins (IDP) that fold upon binding retain conformational heterogeneity in IDP-target complexes. The thermodynamics of such fuzzy interactions is poorly understood. Here we introduce a thermodynamic framework, based on analysis of ITC and CD spectroscopy data, that provides experimental description of IDP association in terms of folding and binding contributions which can be predicted using sequence folding propensities and molecular modeling. We show how IDP can modulate the entropy and enthalpy by adapting their bound-state structural ensemble to achieve optimal binding...
September 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28912275/nmr-reveals-the-intrinsically-disordered-domain-2-of-ns5a-protein-as-an-allosteric-regulator-of-the-hepatitis-c-virus-rna-polymerase-ns5b
#17
Luiza M Bessa, Hélène Launay, Marie Dujardin, François-Xavier Cantrelle, Guy Lippens, Isabelle Landrieu, Robert Schneider, Xavier Hanoulle
Non-structural protein 5B (NS5B) is the RNAdependent RNA polymerase that catalyses replication of the hepatitis C virus (HCV) RNA genome, and so is central for its life cycle. NS5B interacts with the intrinsically disordered domain 2 of NS5A (NS5A-D2), another essential multifunctional HCV protein that is required for RNA replication. As a result, these two proteins represent important targets for anti-HCV chemotherapies. Despite this importance and the existence of NS5B crystal structures, our understanding of the conformational and dynamic behaviour of NS5B in solution and its relationship with NS5A-D2 remain incomplete...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28905237/-1-h-13-c-and-15-n-assignments-of-the-c-terminal-intrinsically-disordered-cytosolic-fragment-of-the-receptor-tyrosine-kinase-erbb2
#18
YingHui Wang, Louise Pinet, Nadine Assrir, Latifa Elantak, Françoise Guerlesquin, Ali Badache, Ewen Lescop, Carine van Heijenoort
ErbB2 (or HER2) is a receptor tyrosine kinase that is involved in signaling pathways controlling cell division, motility and apoptosis. Though important in development and cell growth homeostasis, this protein, when overexpressed, participates in triggering aggressive HER2+ breast cancers. It is composed of an extracellular part and a transmembrane domain, both important for activation by dimerization, and a cytosolic tyrosine kinase, which activates its intrinsically disordered C-terminal end (CtErbB2). Little is known about this C-terminal part of 268 residues, despite its crucial role in interacting with adaptor proteins involved in signaling...
September 13, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28904001/kv3-channels-enablers-of-rapid-firing-neurotransmitter-release-and-neuronal-endurance
#19
REVIEW
Leonard K Kaczmarek, Yalan Zhang
The intrinsic electrical characteristics of different types of neurons are shaped by the K(+) channels they express. From among the more than 70 different K(+) channel genes expressed in neurons, Kv3 family voltage-dependent K(+) channels are uniquely associated with the ability of certain neurons to fire action potentials and to release neurotransmitter at high rates of up to 1,000 Hz. In general, the four Kv3 channels Kv3.1-Kv3.4 share the property of activating and deactivating rapidly at potentials more positive than other channels...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28903561/enhanced-sampling-of-intrinsic-structural-heterogeneity-of-the-bh3-only-protein-binding-interface-of-bcl-xl
#20
Xiaorong Liu, Zhiguang Jia, Jianhan Chen
Anti-apoptotic Bcl-xL plays central roles in regulating programed cell death. Partial unfolding of Bcl-xL has been observed at the interface upon specific binding to the pro-apoptotic BH3-only protein PUMA, which in turn disrupts the interaction of Bcl-xL with tumor suppressor p53 and promotes apoptosis. Previous analysis of existing Bcl-xL structures and atomistic molecular dynamics (MD) simulations have suggested that substantial intrinsic structure heterogeneity exists at the BH3-only protein binding interface of Bcl-xL to facilitate its conformational transitions upon binding...
September 13, 2017: Journal of Physical Chemistry. B
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