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Intrinsically disordered protein

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https://www.readbyqxmd.com/read/29341926/direct-detection-of-carbon-and-nitrogen-nuclei-for-high-resolution-analysis-of-intrinsically-disordered-proteins-using-nmr-spectroscopy
#1
E B Gibbs, R W Kriwacki
Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique for characterizing the structural and dynamic properties of intrinsically disordered proteins and protein regions (IDPs & IDRs). However, the application of NMR to IDPs has been limited by poor chemical shift dispersion in two-dimensional (2D) 1H-15N heteronuclear correlation spectra. Among the various detection schemes available for heteronuclear correlation spectroscopy, 13C direct-detection has become a mainstay for investigations of IDPs owing to the favorable chemical shift dispersion in 2D 13C'-15N correlation spectra...
January 13, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29341251/residue-packing-in-globular-and-intrinsically-disordered-proteins
#2
Rasim Murat Aydinkal, Elife Zerrin Bagci
Intrinsically disordered proteins/regions do not have well-defined secondary and tertiary structures, however, they are functional and it is critical to gain a deep understanding of their residue packing. The shape distributions methodology, which is usually utilized in pattern recognition, clustering and classification studies in computer science, may be adopted to study the residue packing of the proteins. In this study, shape distributions of the globular proteins and intrinsically disordered proteins (IDPs) were obtained to shed light on the residue packing of their structures...
January 17, 2018: Proteins
https://www.readbyqxmd.com/read/29339797/a-brave-new-world-of-rna-binding-proteins
#3
REVIEW
Matthias W Hentze, Alfredo Castello, Thomas Schwarzl, Thomas Preiss
RNA-binding proteins (RBPs) are typically thought of as proteins that bind RNA through one or multiple globular RNA-binding domains (RBDs) and change the fate or function of the bound RNAs. Several hundred such RBPs have been discovered and investigated over the years. Recent proteome-wide studies have more than doubled the number of proteins implicated in RNA binding and uncovered hundreds of additional RBPs lacking conventional RBDs. In this Review, we discuss these new RBPs and the emerging understanding of their unexpected modes of RNA binding, which can be mediated by intrinsically disordered regions, protein-protein interaction interfaces and enzymatic cores, among others...
January 17, 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29339216/in-vivo-biotinylated-calpastatin-improves-the-affinity-purification-of-human-m-calpain
#4
Hung Huy Nguyen, Alexander N Volkov, Guy Vandenbussche, Peter Tompa, Kris Pauwels
Recently we established a novel affinity purification method for calpain by exploiting the specific and reversible binding properties of its intrinsically disordered protein inhibitor, calpastatin. The immobilization strategy relied on the strength and specificity of the biotin - streptavidin interaction. Here, we report an improved and optimized method that even enables the general applicability of in vivo biotinylated (intrinsically disordered) proteins in any affinity capture strategy. Since in vitro chemical biotinylation is only accomplished with reagents that lack exact site specificity, it can not only cause sample heterogeneity but it can also hamper the functionality of the biotinylated molecules...
January 12, 2018: Protein Expression and Purification
https://www.readbyqxmd.com/read/29339192/tissue-specific-differences-in-mitochondrial-dna-maintenance-and-expression
#5
Elena Herbers, Nina J Kekäläinen, Anu Hangas, Jaakko L Pohjoismäki, Steffi Goffart
The different cell types of multicellular organisms have specialized physiological requirements, affecting also their mitochondrial energy production and metabolism. The genome of mitochondria is essential for mitochondrial oxidative phosphorylation (OXHPOS) and thus plays a central role in many human mitochondrial pathologies. Disorders affecting mitochondrial DNA (mtDNA) maintenance are typically resulting in a tissue-specific pattern of mtDNA deletions and rearrangements. Despite this role in disease as well as a biomarker of mitochondrial biogenesis, the tissue-specific parameters of mitochondrial DNA maintenance have been virtually unexplored...
January 12, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29337218/calcium-dependent-disorder-to-order-transitions-are-central-to-the-secretion-and-folding-of-the-cyaa-toxin-of-bordetella-pertussis-the-causative-agent-of-whooping-cough
#6
Darragh P O'Brien, Ana Cristina Sotomayor Perez, Johanna Karst, Sara E Cannella, Véronique Yvette Ntsogo Enguéné, Audrey Hessel, Dorothée Raoux-Barbot, Alexis Voegele, Orso Subrini, Marilyne Davi, J Inaki Guijarro, Bertrand Raynal, Bruno Baron, Patrick England, Belen Hernandez, Mahmoud Ghomi, Véronique Hourdel, Christian Malosse, Julia Chamot-Rooke, Patrice Vachette, Dominique Durand, Sébastien Brier, Daniel Ladant, Alexandre Chenal
The adenylate cyclase toxin (CyaA) plays an essential role in the early stages of respiratory tract colonization by Bordetella pertussis, the causative agent of whooping cough. Once secreted, CyaA invades eukaryotic cells, leading to cell death. The cell intoxication process involves a unique mechanism of translocation of the CyaA catalytic domain directly across the plasma membrane of the target cell. Herein, we review our recent results describing how calcium is involved in several steps of this intoxication process...
January 11, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29334167/cross-linking-mass-spectrometry-for-studying-protein-structures-and-protein-protein-interactions-where-are-we-now-and-where-should-we-go-from-here
#7
Andrea Sinz
Structural mass spectrometry (MS) is gaining increasing importance in deriving valuable three-dimensional structural information on proteins and protein complexes and complements existing techniques, such as NMR spectroscopy and X-ray crystallography. Structural MS unites different MS-based techniques, i.e, hydrogen-deuterium exchange, native MS, ion-mobility MS, protein footprinting, and chemical cross-linking/MS, and allows fundamental questions in structural biology to be addressed. In this article, I will focus on the cross-linking/MS strategy...
January 15, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29331721/understanding-protein-drug-interactions-using-ion-mobility-mass-spectrometry
#8
REVIEW
Claire E Eyers, Matthias Vonderach, Samantha Ferries, Kiani Jeacock, Patrick A Eyers
Ion mobility-mass spectrometry (IM-MS) is an important addition to the analytical toolbox for the structural evaluation of proteins, and is enhancing many areas of biophysical analysis. Disease-associated proteins, including enzymes such as protein kinases, transcription factors exemplified by p53, and intrinsically disordered proteins, including those prone to aggregation, are all amenable to structural analysis by IM-MS. In this review we discuss how this powerful technique can be used to understand protein conformational dynamics and aggregation pathways, and in particular, the effect that small molecules, including clinically-relevant drugs, play in these processes...
January 10, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29330519/large-scale-aggregation-analysis-of-eukaryotic-proteins-reveals-an-involvement-of-intrinsically-disordered-regions-in-protein-folding
#9
Eri Uemura, Tatsuya Niwa, Shintaro Minami, Kazuhiro Takemoto, Satoshi Fukuchi, Kodai Machida, Hiroaki Imataka, Takuya Ueda, Motonori Ota, Hideki Taguchi
A subset of the proteome is prone to aggregate formation, which is prevented by chaperones in the cell. To investigate whether the basic principle underlying the aggregation process is common in prokaryotes and eukaryotes, we conducted a large-scale aggregation analysis of ~500 cytosolic budding yeast proteins using a chaperone-free reconstituted translation system, and compared the obtained data with that of ~3,000 Escherichia coli proteins reported previously. Although the physicochemical properties affecting the aggregation propensity were generally similar in yeast and E...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330047/an-intrinsically-disordered-domain-in-polaribacter-irgensii-kopri-22228-cspb-confers-extraordinary-freeze-tolerance
#10
Youn Hong Jung, Ji-Hyun Uh, Kyunghee Lee, Hana Im
Organisms living in extremely cold environments possess mechanisms to survive low temperatures. Among the known cold-induced genes, cold-shock proteins (Csps) are the most prominent. A csp-homologous gene, cspBPi, has been cloned from the Arctic bacterium Polaribacter irgensii KOPRI 22228, and overexpression of this gene greatly increased the freezing tolerance of its host. This protein consists of a unique N-terminal domain and a well conserved C-terminal cold shock domain. To elucidate the detailed mechanisms involved in the extraordinary freeze-tolerance conferred by CspBPi, we identified the responsible domain by mutational analysis...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29329397/minar1-is-a-notch2-binding-protein-that-inhibits-angiogenesis-and-breast-cancer-growth
#11
Rachel Xi-Yeen Ho, Rosana D Meyer, Kevin B Chandler, Esma Ersoy, Michael Park, Philip A Bondzie, Nima Rahimi, Huihong Xu, Catherine E Costello, Nader Rahimi
Intrinsically disordered proteins (IDPs)/intrinsically unstructured proteins (IUPs) are characterized by the lack of fixed or stable tertiary structure, and are increasingly recognized as an important class of proteins with major roles in signal transduction and transcriptional regulation. In this study, we report the identification and functional characterization of a previously uncharacterized protein (UPF0258/KIAA1024), major intrinsically disordered Notch2-associated receptor 1 (MINAR1). While MINAR1 carries a single transmembrane domain and a short cytoplasmic domain, it has a large extracellular domain that shares no similarity with known protein sequences...
January 10, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29327340/shank3-deficient-thalamocortical-neurons-show-hcn-channelopathy-and-alterations-in-intrinsic-electrical-properties
#12
Mengye Zhu, VinayKumar Idikuda, Jianbing Wang, Fusheng Wei, Virang Kumar, Nikhil Shah, Christopher B Waite, Qinglian Liu, Lei Zhou
Shank3 is a scaffolding protein that is highly enriched in excitatory synapses. Mutations in Shank3 gene have been linked to neuropsychiatric disorders especially the Autism Spectrum Disorders (ASD). Shank3 deficiency is known to cause impairments in synaptic transmission, but its effects on basic neuronal electrical properties that are more localized to the soma and proximal dendrites remain unclear. Here we confirmed that in heterologous expression systems two different Shank3 isoforms, Shank3A and Shank3C, significant increase the surface expression of the hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channel...
January 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29326986/measles-virus-background-and-oncolytic-virotherapy
#13
REVIEW
Sankhajit Bhattacharjee, Pramod Kumar Yadava
Measles is a highly transmissible disease caused by measles virus and remains a major cause of child mortality in developing countries. Measles virus nucleoprotein (N) encapsidates the RNA genome of the virus for providing protection from host cell endonucleases and for specific recognition of viral RNA as template for transcription and replication. This protein is over-expressed at the time of viral replication. The C-terminal of N protein is intrinsically disordered, which enables this protein to interact with several host cell proteins...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29320696/using-a-fret-library-with-multiple-probe-pairs-to%C3%A2-drive-monte-carlo-simulations-of-%C3%AE-synuclein
#14
John J Ferrie, Conor M Haney, Jimin Yoon, Buyan Pan, Yi-Chih Lin, Zahra Fakhraai, Elizabeth Rhoades, Abhinav Nath, E James Petersson
We describe a strategy for experimentally-constraining computational simulations of intrinsically disordered proteins (IDPs), using α-synuclein, an IDP with a central role in Parkinson's disease pathology, as an example. Previously, data from single-molecule Förster Resonance Energy Transfer (FRET) experiments have been effectively utilized to generate experimentally constrained computational models of IDPs. However, the fluorophores required for single-molecule FRET experiments are not amenable to the study of short-range (<30 Å) interactions...
January 9, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29315236/understanding-the-role-of-intrinsic-disorder-of-viral-proteins-in-the-oncogenicity-of-different-types-of-hpv
#15
Elvira Regina Tamarozzi, Silvana Giuliatti
Intrinsic disorder is very important in the biological function of several proteins, and is directly linked to their foldability during interaction with their targets. There is a close relationship between the intrinsically disordered proteins and the process of carcinogenesis involving viral pathogens. Among these pathogens, we have highlighted the human papillomavirus (HPV) in this study. HPV is currently among the most common sexually transmitted infections, besides being the cause of several types of cancer...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29314619/naringin-protects-pancreatic-%C3%AE-cells-against-oxidative-stress-induced-apoptosis-by-inhibiting-both-intrinsic-and-extrinsic-pathways-in-insulin-deficient-diabetic-mice
#16
Ye Jin Lim, Jung Ho Kim, Jeong Hoon Pan, Jae Kyeom Kim, Tae-Sik Park, Young Jun Kim, Jin Hyup Lee, Jun Ho Kim
SCOPE: Oxidative stress has been suggested to play a central role in the pathogenesis of diabetes, as well as other metabolic disorders. Naringin, a major flavanone glycoside in citrus species, has been shown to display strong antioxidant potential in in vitro and in vivo models of oxidative stress; however, the underlying protective mechanisms in diabetes are unclear. METHODS AND RESULTS: To study the protective effects and molecular mechanisms of naringin in preventing islet dysfunction and diabetes, we examined glucose homeostasis, β-cell apoptosis, and inflammatory response in insulin-deficient diabetic mice exposed to acute oxidative stress with streptozotocin (STZ)...
January 4, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29314492/the-binding-mode-of-a-repeat-like-tau-sequence-with-tubulin
#17
Harindranath Kadavath, Yunior Cabrales Fontela, Mariusz Jaremko, Lukasz Jaremko, Kerstin Overkamp, Jacek Biernat, Eckhard Mandelkow, Markus Zweckstetter
The microtubule-associated protein Tau promotes the polymerization of tubulin and modulates the function of microtubules. Because of the dynamic nature of the Tau/tubulin interaction, the structural basis of this complex has remained largely elusive. Using a combination of NMR methods optimized for ligand-receptor interactions and site-directed mutagenesis we demonstrate that the flanking domain downstream of the four microtubule-binding repeats of Tau binds competitively to a site on the α-tubulin surface...
January 3, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29314274/small-angle-x-ray-scattering-and-cross-linking-for-data-assisted-protein-structure-prediction-in-casp-12-with-prospects-for-improved-accuracy
#18
Tadeusz L Ogorzalek, Greg L Hura, Adam Belsom, Kathryn H Burnett, Andriy Kryshtafovych, John A Tainer, Juri Rappsilber, Susan E Tsutakawa, Krzysztof Fidelis
Experimental data offers empowering constraints for structure prediction. These constraints can be used to filter equivalently scored models or more powerfully within optimization functions toward prediction. In CASP12, Small Angle X-ray Scattering (SAXS) and Cross-Linking Mass Spectrometry (CLMS) data, measured on an exemplary set of novel fold targets, were provided to the CASP community of protein structure predictors. As HT, solution-based techniques, SAXS and CLMS can efficiently measure states of the full-length sequence in its native solution conformation and assembly...
January 4, 2018: Proteins
https://www.readbyqxmd.com/read/29313812/pathogenic-commonalities-between-spinal-muscular-atrophy-and-amyotrophic-lateral-sclerosis-converging-roads-to-therapeutic-development
#19
REVIEW
Melissa Bowerman, Lyndsay M Murrray, Frédérique Scamps, Bernard L Schneider, Rashmi Kothary, Cédric Raoul
Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are the two most common motoneuron disorders, which share typical pathological hallmarks while remaining genetically distinct. Indeed, SMA is caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene whilst ALS, albeit being mostly sporadic, can also be caused by mutations within genes, including superoxide dismutase 1 (SOD1), Fused in Sarcoma (FUS), TAR DNA-binding protein 43 (TDP-43) and chromosome 9 open reading frame 72 (C9ORF72)...
December 4, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29307002/unified-understanding-of-folding-and-binding-mechanisms-of-globular-and-intrinsically-disordered-proteins
#20
REVIEW
Munehito Arai
Extensive experimental and theoretical studies have advanced our understanding of the mechanisms of folding and binding of globular proteins, and coupled folding and binding of intrinsically disordered proteins (IDPs). The forces responsible for conformational changes and binding are common in both proteins; however, these mechanisms have been separately discussed. Here, we attempt to integrate the mechanisms of coupled folding and binding of IDPs, folding of small and multi-subdomain proteins, folding of multimeric proteins, and ligand binding of globular proteins in terms of conformational selection and induced-fit mechanisms as well as the nucleation-condensation mechanism that is intermediate between them...
January 6, 2018: Biophysical Reviews
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