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https://www.readbyqxmd.com/read/27915351/the-role-of-nephrologist-in-the-intensive-care-unit
#1
Zoltán H Endre
Participation by nephrologists is needed in most intensive care units, even when such units are 'closed'. This participation should assist with diagnosis and management of intrinsic and complex renal diseases such as vasculitis, complex metabolic and electrolyte disorders including hyponatremia, and acute kidney injury (AKI) with and without underlying chronic kidney disease (CKD). Early nephrologist involvement will also facilitate transition to continuing care and follow-up after an episode of AKI, but may also assist in avoiding dialysis where treatment is futile...
December 3, 2016: Blood Purification
https://www.readbyqxmd.com/read/27915289/codon-usage-is-less-optimized-in-eukaryotic-gene-segments-encoding-intrinsically-disordered-regions-than-in-those-encoding-structural-domains
#2
Keiichi Homma, Tamotsu Noguchi, Satoshi Fukuchi
Codon usage tends to be optimized in highly expressed genes. A plausible explanation for this phenomenon is that translational accuracy is increased in highly expressed genes with infrequent use of rare codons. Besides structural domains (SDs), eukaryotic proteins generally have intrinsically disordered regions (IDRs) that by themselves do not assume unique three-dimensional structures. As IDRs are free from structural constraint, they can probably accommodate more translational errors than SDs can. Thus, codon usage in IDRs is likely to be less optimized than that in SDs...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27915233/molecular-basis-for-the-autonomous-promotion-of-cell-proliferation-by-angiogenin
#3
Trish T Hoang, Ronald T Raines
Canonical growth factors act indirectly via receptor-mediated signal transduction pathways. Here, we report on an autonomous pathway in which a growth factor is internalized, has its localization regulated by phosphorylation, and ultimately uses intrinsic catalytic activity to effect epigenetic change. Angiogenin (ANG), a secreted vertebrate ribonuclease, is known to promote cell proliferation, leading to neovascularization as well as neuroprotection in mammals. Upon entering cells, ANG encounters the cytosolic ribonuclease inhibitor protein, which binds with femtomolar affinity...
December 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27914198/spatial-patterning-of-p-granules-by-rna-induced-phase-separation-of-the-intrinsically-disordered-protein-meg-3
#4
Jarrett Smith, Deepika Calidas, Helen Schmidt, Tu Lu, Dominique Rasoloson, Geraldine Seydoux
RNA granules are non-membrane bound cellular compartments that contain RNA and RNA binding proteins. The molecular mechanisms that regulate the spatial distribution of RNA granules in cells are poorly understood. During polarization of the C. elegans zygote, germline RNA granules, called P granules, assemble preferentially in the posterior cytoplasm. We present evidence that P granule asymmetry depends on RNA-induced phase separation of the granule scaffold MEG-3. MEG-3 is an intrinsically disordered protein that binds and phase separates with RNA in vitro...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27913731/disentangling-polydispersity-in-the-pcna-p15paf-complex-a-disordered-transient-and-multivalent-macromolecular-assembly
#5
Tiago N Cordeiro, Po-Chia Chen, Alfredo De Biasio, Nathalie Sibille, Francisco J Blanco, Jochen S Hub, Ramon Crehuet, Pau Bernadó
The intrinsically disordered p15(PAF) regulates DNA replication and repair when interacting with the Proliferating Cell Nuclear Antigen (PCNA) sliding clamp. As many interactions between disordered proteins and globular partners involved in signaling and regulation, the complex between p15(PAF) and trimeric PCNA is of low affinity, forming a transient complex that is difficult to characterize at a structural level due to its inherent polydispersity. We have determined the structure, conformational fluctuations, and relative population of the five species that coexist in solution by combining small-angle X-ray scattering (SAXS) with molecular modelling...
December 1, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27911791/a-functional-role-for-intrinsic-disorder-in-the-tau-tubulin-complex
#6
Ana M Melo, Juliana Coraor, Garrett Alpha-Cobb, Shana Elbaum-Garfinkle, Abhinav Nath, Elizabeth Rhoades
Tau is an intrinsically disordered protein with an important role in maintaining the dynamic instability of neuronal microtubules. Despite intensive study, a detailed understanding of the functional mechanism of tau is lacking. Here, we address this deficiency by using intramolecular single-molecule Förster Resonance Energy Transfer (smFRET) to characterize the conformational ensemble of tau bound to soluble tubulin heterodimers. Tau adopts an open conformation on binding tubulin, in which the long-range contacts between both termini and the microtubule binding region that characterize its compact solution structure are diminished...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911701/the-contribution-of-intrinsically-disordered-regions-to-protein-function-cellular-complexity-and-human-disease
#7
REVIEW
M Madan Babu
In the 1960s, Christian Anfinsen postulated that the unique three-dimensional structure of a protein is determined by its amino acid sequence. This work laid the foundation for the sequence-structure-function paradigm, which states that the sequence of a protein determines its structure, and structure determines function. However, a class of polypeptide segments called intrinsically disordered regions does not conform to this postulate. In this review, I will first describe established and emerging ideas about how disordered regions contribute to protein function...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27910948/improved-in-cell-structure-determination-of-proteins-at-near-physiological-concentration
#8
Teppei Ikeya, Tomomi Hanashima, Saori Hosoya, Manato Shimazaki, Shiro Ikeda, Masaki Mishima, Peter Güntert, Yutaka Ito
Investigating three-dimensional (3D) structures of proteins in living cells by in-cell nuclear magnetic resonance (NMR) spectroscopy opens an avenue towards understanding the structural basis of their functions and physical properties under physiological conditions inside cells. In-cell NMR provides data at atomic resolution non-invasively, and has been used to detect protein-protein interactions, thermodynamics of protein stability, the behavior of intrinsically disordered proteins, etc. in cells. However, so far only a single de novo 3D protein structure could be determined based on data derived only from in-cell NMR...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27908782/adaptive-responses-of-neuronal-mitochondria-to-bioenergetic-challenges-roles-in-neuroplasticity-and-disease-resistance
#9
REVIEW
Sophia M Raefsky, Mark P Mattson
An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27905618/mechanism-of-%C3%AE-synuclein-translocation-through-a-vdac-nanopore-revealed-by-energy-landscape-modeling-of-escape-time-distributions
#10
David P Hoogerheide, Philip A Gurnev, Tatiana K Rostovtseva, Sergey M Bezrukov
We probe the energy landscape governing the passage of α-synuclein, a natural "diblock copolymer"-like polypeptide, through a nanoscale pore. α-Synuclein is an intrinsically disordered neuronal protein associated with Parkinson's pathology. The motion of this electrically heterogeneous polymer in the β-barrel voltage-dependent anion channel (VDAC) of the mitochondrial outer membrane strongly depends on the properties of both the charged and uncharged regions of the α-synuclein polymer. We model this motion in two ways...
December 1, 2016: Nanoscale
https://www.readbyqxmd.com/read/27902336/characterization-of-the-banana-streak-virus-capsid-protein-and-mapping-of-the-immunodominant-continuous-b-cell-epitopes-to-the-surface-exposed-n-terminus
#11
Jenny Vo, Paul Campbell, Nur N Mahfuzc, Ras Ramli, Daniel Pagendam, Ross Barnard, Andrew Geering
This study identified the structural proteins of two badnavirus species, Banana streak MY virus (BSMYV) and Banana streak OL virus (BSOLV), and mapped the distribution of continuous B-cell epitopes. Two different CP isoforms of about 44 and 40 kDa (CP1 and CP2) and the virion-associated protein (VAP) were consistently associated with purified virions. For both viral species, the N-terminus of CP2 was successfully sequenced by Edman degradation but that of CP1 was chemically blocked. De novo peptide sequencing of tryptic digests suggested that CP1 and CP2 derive from the same region of the P3 polyprotein but differ in the length of either the N- or C-terminus...
October 24, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901068/nanomechanical-properties-of-distinct-fibrillar-polymorphs-of-the-protein-%C3%AE-synuclein
#12
Ali Makky, Luc Bousset, Jérôme Polesel-Maris, Ronald Melki
Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson's disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899635/interpro-in-2017-beyond-protein-family-and-domain-annotations
#13
Robert D Finn, Teresa K Attwood, Patricia C Babbitt, Alex Bateman, Peer Bork, Alan J Bridge, Hsin-Yu Chang, Zsuzsanna Dosztányi, Sara El-Gebali, Matthew Fraser, Julian Gough, David Haft, Gemma L Holliday, Hongzhan Huang, Xiaosong Huang, Ivica Letunic, Rodrigo Lopez, Shennan Lu, Aron Marchler-Bauer, Huaiyu Mi, Jaina Mistry, Darren A Natale, Marco Necci, Gift Nuka, Christine A Orengo, Youngmi Park, Sebastien Pesseat, Damiano Piovesan, Simon C Potter, Neil D Rawlings, Nicole Redaschi, Lorna Richardson, Catherine Rivoire, Amaia Sangrador-Vegas, Christian Sigrist, Ian Sillitoe, Ben Smithers, Silvano Squizzato, Granger Sutton, Narmada Thanki, Paul D Thomas, Silvio C E Tosatto, Cathy H Wu, Ioannis Xenarios, Lai-Su Yeh, Siew-Yit Young, Alex L Mitchell
InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899601/disprot-7-0-a-major-update-of-the-database-of-disordered-proteins
#14
Damiano Piovesan, Francesco Tabaro, Ivan Mičetić, Marco Necci, Federica Quaglia, Christopher J Oldfield, Maria Cristina Aspromonte, Norman E Davey, Radoslav Davidović, Zsuzsanna Dosztányi, Arne Elofsson, Alessandra Gasparini, András Hatos, Andrey V Kajava, Lajos Kalmar, Emanuela Leonardi, Tamas Lazar, Sandra Macedo-Ribeiro, Mauricio Macossay-Castillo, Attila Meszaros, Giovanni Minervini, Nikoletta Murvai, Jordi Pujols, Daniel B Roche, Edoardo Salladini, Eva Schad, Antoine Schramm, Beata Szabo, Agnes Tantos, Fiorella Tonello, Konstantinos D Tsirigos, Nevena Veljković, Salvador Ventura, Wim Vranken, Per Warholm, Vladimir N Uversky, A Keith Dunker, Sonia Longhi, Peter Tompa, Silvio C E Tosatto
The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007. The current release holds information on more than 800 entries of IDPs/IDRs, i.e. intrinsically disordered proteins or regions that exist and function without a well-defined three-dimensional structure. We have re-curated previous entries to purge DisProt from conflicting cases, and also upgraded the functional classification scheme to reflect continuous advance in the field in the past 10 years or so...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899135/analysis-of-pvama1-genes-from-china-myanmar-border-reveals-little-regional-genetic-differentiation-of-plasmodium-vivax-populations
#15
Xiaotong Zhu, Pan Zhao, Si Wang, Fei Liu, Jun Liu, Jian Wang, Zhaoqing Yang, Guiyun Yan, Qi Fan, Yaming Cao, Liwang Cui
BACKGROUND: With the premise of diminishing parasite genetic diversity following the reduction of malaria incidence, the analysis of polymorphic antigenic markers may provide important information about the impact of malaria control on local parasite populations. Here we evaluated the genetic diversity of Plasmodium vivax apical membrane antigen 1 (Pvama1) gene in a parasite population from the China-Myanmar border and compared it with global P. vivax populations. METHODS: We performed evolutionary analysis to examine the genetic diversity, natural selection, and population differentiation of 73 Pvama1 sequences acquired from the China-Myanmar border as well as 615 publically available Pvama1 sequences from seven global P...
November 29, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27897373/an-integrated-mass-spectrometry-based-approach-to-probe-the-structure-of-the-full-length-wild-type-tetrameric-p53-tumor-suppressor
#16
Christian Arlt, Vanessa Flegler, Christian H Ihling, Mathias Schäfer, Iris Thondorf, Andrea Sinz
We present an integrated approach for investigating the topology of proteins through native mass spectrometry (MS) and cross-linking/MS, which we applied to the full-length wild-type p53 tetramer. For the first time, the two techniques were combined in one workflow to obtain not only structural insight in the p53 tetramer, but also information on the cross-linking efficiency and the impact of cross-linker modification on the conformation of an intrinsically disordered protein (IDP). P53 cross-linking was monitored by native MS and as such, our strategy serves as a quality control for different cross-linking reagents...
November 29, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27894241/a-novel-relationship-for-schizophrenia-bipolar-and-major-depressive-disorder-part-6-a-hint-from-chromosome-6-high-density-association-screen
#17
X Chen, F Long, B Cai, X Chen, G Chen
Convergent evidence from genetics, symptomatology and psychopharmacology imply that there are intrinsic connections between schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD), for example, any two or even three of these disorders could co-exist in some families. A total of 56.400 single nucleotide polymorphism (SNPs) on chromosome 6 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (type-I), 177 MDD patients and 1000 controls. Associated SNP loci on chromosome 6 were comprehensively revealed and outstanding susceptibility genes were identified including JARID2 (Homo sapiens jumonji, AT rich interactive domain 2) which plays an essential role in embryonic development and neural tube fusion process...
November 28, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27891621/animal-cryptochromes-divergent-roles-in-light-perception-circadian-timekeeping-and-beyond
#18
Alicia K Michael, Jennifer L Fribourgh, Russell N Van Gelder, Carrie L Partch
Cryptochromes are evolutionarily related to the light-dependent DNA repair enzyme photolyase, serving as major regulators of circadian rhythms in insects and vertebrate animals. There are two types of cryptochromes in the animal kingdom: Drosophila-like CRYs that act as non-visual photopigments linking circadian rhythms to the environmental light/dark cycle, and vertebrate-like CRYs that do not appear to sense light directly, but control the generation of circadian rhythms by acting as transcriptional repressors...
November 28, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27890856/sirna-cell-penetrating-peptides-complexes-as-a-combinatorial-therapy-against-chronic-myeloid-leukemia-using-bv173-cell-line-as-model
#19
João Miguel Freire, Inês Rego de Figueiredo, Javier Valle, Ana Salomé Veiga, David Andreu, Francisco J Enguita, Miguel A R B Castanho
Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by a single gene mutation, a reciprocal translocation that originates the Bcr-Abl gene with constitutive tyrosine kinase activity. As a monogenic disease, it is an optimum target for RNA silencing therapy. We developed a siRNA-based therapeutic approach in which the siRNA is delivered by pepM or pepR, two cell-penetrating peptides (CPPs) derived from the dengue virus capsid (DENV C) protein. These peptides have a dual role: siRNA delivery into cells and direct action as bioportides, i...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27890828/alterations-of-motor-cortical-microcircuit-in-a-depressive-like-mouse-model-produced-by-light-deprivation
#20
Yun-Feng Zhang, Qi-Qin Li, Jia Qu, Cui-Min Sun, Yun Wang
Depression is one of the most prevalent and life-threatening forms of mental illness. The heavy social burden imposed by this disorder calls for a better understanding of its pathogenesis. Light deficiency is an important factor potentially leading to depression. However, how the light deficiency affects neural microcircuit underlying depression remains largely unknown. This study investigated the properties of morphology, electrophysiology, and synaptology of layer V pyramidal cells (L5PCs) in the motor cortex of a mouse model with depressive behavioral phenotype that was produced by light deprivation (LD)...
November 25, 2016: Neuroscience
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