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Intrinsically disordered protein

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https://www.readbyqxmd.com/read/28729736/the-relationship-between-folding-and-activity-in-ureg-an-intrinsically-disordered-enzyme
#1
Marta Palombo, Alessio Bonucci, Emilien Etienne, Stefano Ciurli, Vladimir N Uversky, Bruno Guigliarelli, Valérie Belle, Elisabetta Mileo, Barbara Zambelli
A growing body of literature on intrinsically disordered proteins (IDPs) led scientists to rethink the structure-function paradigm of protein folding. Enzymes are often considered an exception to the rule of intrinsic disorder (ID), believed to require a unique structure for catalysis. However, recent studies revealed the presence of disorder in several functional native enzymes. In the present work, we address the importance of dynamics for catalysis, by investigating the relationship between folding and activity in Sporosarcina pasteurii UreG (SpUreG), a P-loop GTPase and the first discovered native ID enzyme, involved in the maturation of the nickel-containing urease...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726779/maml1-acts-cooperatively-with-gli-proteins-to-regulate-sonic-hedgehog-signaling-pathway
#2
Roberta Quaranta, Maria Pelullo, Sabrina Zema, Francesca Nardozza, Saula Checquolo, Dieter Matthias Lauer, Francesca Bufalieri, Rocco Palermo, Maria Pia Felli, Alessandra Vacca, Claudio Talora, Lucia Di Marcotullio, Isabella Screpanti, Diana Bellavia
Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule cell progenitors (GCPs) and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma. The effects of Shh pathway are mediated by the Gli family of transcription factors, which controls the expression of a number of target genes, including Gli1. Here, we identify Mastermind-like 1 (Maml1) as a novel regulator of the Shh signaling since it interacts with Gli proteins, working as a potent transcriptional coactivator...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28720707/intrinsically-disordered-chromatin-protein-nupr1-binds-to-the-c-terminal-region-of-polycomb-ring1b
#3
Patricia Santofimia-Castaño, Bruno Rizzuti, Ángel L Pey, Philippe Soubeyran, Miguel Vidal, Raúl Urrutia, Juan L Iovanna, José L Neira
Intrinsically disordered proteins (IDPs) are ubiquitous in eukaryotes, and they are often associated with diseases in humans. The protein NUPR1 is a multifunctional IDP involved in chromatin remodeling and in the development and progression of pancreatic cancer; however, the details of such functions are unknown. Polycomb proteins are involved in specific transcriptional cascades and gene silencing. One of the proteins of the Polycomb complex is the Ring finger protein 1 (RING1). RING1 is related to aggressive tumor features in multiple cancer types...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28719664/predicting-the-protein-half-life-in-tissue-from-its-cellular-properties
#4
Mahbubur Rahman, Rovshan G Sadygov
Protein half-life is an important feature of protein homeostasis (proteostasis). The increasing number of in vivo and in vitro studies using high throughput proteomics provide estimates of the protein half-lives in tissues and cells. However, protein half-lives in cells and tissues are different. Due to the resource requirements for researching tissues, more data is available from cellular studies than tissues. We have designed a multivariate linear model for predicting protein half-life in tissue from its cellular properties...
2017: PloS One
https://www.readbyqxmd.com/read/28719185/small-molecule-enhancement-of-20s-proteasome-activity-targets-intrinsically-disordered-proteins
#5
Corey L Jones, Evert Njomen, Benita Sjogren, Thomas S Dexheimer, Jetze J Tepe
The 20S proteasome is the main protease for degradation of oxidatively damaged and intrinsically disordered proteins. When accumulation of disordered or oxidatively damaged proteins exceed proper clearance in neurons, imbalanced pathway signaling or aggregation occurs, which have been implicated in the pathogenesis of several neurological disor-ders. Screening of the NIH Clinical Collection and Prestwick libraries identified the neuroleptic agent chlorpromazine as a lead agent capable of enhancing 20S proteasome activity...
July 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28716919/decoupling-of-size-and-shape-fluctuations-in-heteropolymeric-sequences-reconciles-discrepancies-in-saxs-vs-fret-measurements
#6
Gustavo Fuertes, Niccolò Banterle, Kiersten M Ruff, Aritra Chowdhury, Davide Mercadante, Christine Koehler, Michael Kachala, Gemma Estrada Girona, Sigrid Milles, Ankur Mishra, Patrick R Onck, Frauke Gräter, Santiago Esteban-Martín, Rohit V Pappu, Dmitri I Svergun, Edward A Lemke
Unfolded states of proteins and native states of intrinsically disordered proteins (IDPs) populate heterogeneous conformational ensembles in solution. The average sizes of these heterogeneous systems, quantified by the radius of gyration (RG ), can be measured by small-angle X-ray scattering (SAXS). Another parameter, the mean dye-to-dye distance (RE ) for proteins with fluorescently labeled termini, can be estimated using single-molecule Förster resonance energy transfer (smFRET). A number of studies have reported inconsistencies in inferences drawn from the two sets of measurements for the dimensions of unfolded proteins and IDPs in the absence of chemical denaturants...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716441/unraveling-the-meaning-of-chemical-shifts-in-protein-nmr
#7
REVIEW
Mark V Berjanskii, David S Wishart
Chemical shifts are among the most informative parameters in protein NMR. They provide wealth of information about protein secondary and tertiary structure, protein flexibility, and protein-ligand binding. In this report, we review the progress in interpreting and utilizing protein chemical shifts that has occurred over the past 25years, with a particular focus on the large body of work arising from our group and other Canadian NMR laboratories. More specifically, this review focuses on describing, assessing, and providing some historical context for various chemical shift-based methods to: (1) determine protein secondary and super-secondary structure; (2) derive protein torsion angles; (3) assess protein flexibility; (4) predict residue accessible surface area; (5) refine 3D protein structures; (6) determine 3D protein structures and (7) characterize intrinsically disordered proteins...
July 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28714191/disordered-conformation-with-low-pii-helix-in-phosphoproteins-orchestrates-biomimetic-apatite-formation
#8
Melika Sarem, Steffen Lüdeke, Ralf Thomann, Pavel Salavei, Zhaoyong Zou, Wouter Habraken, Admir Masic, V Prasad Shastri
The interplay between noncollagenous proteins and biomineralization is widely accepted, yet the contribution of their secondary structure in mineral formation remains to be clarified. This study demonstrates a role for phosvitin, an intrinsically disordered phosphoprotein, in chick embryo skeletal development, and using circular dichroism and matrix least-squares Henderson-Hasselbalch global fitting, unravels three distinct pH-dependent secondary structures in phosvitin. By sequestering phosvitin on a biomimetic 3D insoluble cationic framework at defined pHs, access is gained to phosvitin in various conformational states...
July 17, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28713368/the-sptransformer-gene-family-formerly-sp185-333-in-the-purple-sea-urchin-and-the-functional-diversity-of-the-anti-pathogen-rsptransformer-e1-protein
#9
REVIEW
L Courtney Smith, Cheng Man Lun
The complex innate immune system of sea urchins is underpinned by several multigene families including the SpTransformer family (SpTrf; formerly Sp185/333) with estimates of ~50 members, although the family size is likely variable among individuals of Strongylocentrotus purpuratus. The genes are small with similar structure, are tightly clustered, and have several types of repeats in the second of two exons and that surround each gene. The density of repeats suggests that the genes are positioned within regions of genomic instability, which may be required to drive sequence diversification...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28710275/a-ph-dependent-switch-promotes-%C3%AE-synuclein-fibril-formation-via-glutamate-residues
#10
Gina M Moriarty, Michael P Olson, Tamr B Atieh, Maria K Janowska, Sagar D Khare, Jean Baum
Alpha-synuclein (αS) is the primary protein associated with Parkinson's disease, and undergoes aggregation from its intrinsically disordered monomeric form to a cross-β fibrillar form. The closely related homolog beta-synuclein (βS) is essentially fibril resistant under cytoplasmic physiological conditions. Toxic gain of function by βS has been linked to dysfunction, but the aggregation behavior of βS under altered pH is not well understood. In this work, we compare fibril formation of αS and βS at pH 7...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28709000/regulatory-expansion-in-mammals-of-multivalent-hnrnp-assemblies-that-globally-control-alternative-splicing
#11
Serge Gueroussov, Robert J Weatheritt, Dave O'Hanlon, Zhen-Yuan Lin, Ashrut Narula, Anne-Claude Gingras, Benjamin J Blencowe
Alternative splicing (AS) patterns have diverged rapidly during vertebrate evolution, yet the functions of most species- and lineage-specific splicing events are not known. We observe that mammalian-specific AS events are enriched in transcript sequences encoding intrinsically disordered regions (IDRs) of proteins, in particular those containing glycine/tyrosine repeats that mediate formation of higher-order protein assemblies implicated in gene regulation and human disease. These evolutionary changes impact nearly all members of the hnRNP A and D families of RNA binding proteins...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28707474/native-hydrophobic-binding-interactions-at-the-transition-state-for-association-between-the-taz1-domain-of-cbp-and-the-disordered-tad-stat2-are-not-a-requirement
#12
Ida Lindström, Jakob Dogan
A significant fraction of the eukaryotic proteome consists of proteins that are either partially or completely disordered in native-like conditions. Intrinsically disordered proteins (IDPs) are common in protein-protein interactions and are involved in numerous cellular processes. Although many proteins have been identified as disordered, much less is known about the binding mechanisms of the coupled binding and folding reactions involving IDPs. Here we have analyzed the rate-limiting transition state for the binding between the TAZ1 domain of CREB binding protein and the intrinsically disordered transactivation domain of STAT2 (TAD-STAT2) by site-directed mutagenesis and kinetic experiments (Φ-value analysis), and found that the native protein-protein binding interface is not formed at the transition state for binding...
July 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28703128/structural-insights-into-the-mycobacteria-transcription-initiation-complex-from-analysis-of-x-ray-crystal-structures
#13
Elizabeth A Hubin, Mirjana Lilic, Seth A Darst, Elizabeth A Campbell
The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the αCTD may play a role in Mtb transcription regulation...
July 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28701416/eukaryotic-transcription-factors-paradigms-of-protein-intrinsic-disorder
#14
REVIEW
Lasse Staby, Charlotte O'Shea, Martin Willemoës, Frederik Theisen, Birthe B Kragelund, Karen Skriver
Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains targeting specific cis-acting elements in genes, and by the significant lack of fixed tertiary structure in their extensive intrinsically disordered regions. Recent research in protein intrinsic disorder (ID) has changed our understanding of transcriptional activation domains from 'negative noodles' to ID regions with function-related, short sequence motifs and molecular recognition features with structural propensities...
July 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28696098/enhanced-binding-affinity-via-destabilization-of-the-unbound-state-a-millisecond-hydrogen-deuterium-exchange-study-of-the-interaction-between-p53-and-a-pleckstrin-homology-domain
#15
Shaolong Zhu, Rahima Khatun, Cristina Lento, Yi Sheng, Derek J Wilson
The incorporation of intrinsically disordered domains enables proteins to engage a wide variety of targets, with phosphorylation often modulating target specificity and affinity. Although phosphorylation can clearly act as a chemical driver of complexation in structured proteins, e.g., by abrogating or permitting new charge-charge interactions, the basis for enhancement of the hydrophobically driven interactions that are typical of disordered protein-target complexation is less clear. To determine how phosphorylation can positively impact target recruitment in disordered domains, we have examined the interaction between the disordered N-terminal transactivation domain (TAD) of p53 and the pleckstrin homology (PH) domain of p62...
July 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28692103/supercharging-spycatcher-toward-an-intrinsically-disordered-protein-with-stimuli-responsive-chemical-reactivity
#16
Yang Cao, Dong Liu, Wen-Bin Zhang
We report a supercharged, intrinsically disordered protein, SpyCatcher(-), possessing stimuli-responsive reactivity toward SpyTag with tunable yields ranging from 4% to 98% depending on pH, temperature, ionic strength, etc. The CD and NMR studies reveal that the reaction occurs through a folded intermediate formed probably via a different mechanism from that of SpyCatcher.
July 10, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28692085/functional-roles-of-intrinsic-disorder-in-crispr-associated-protein-cas9
#17
Zhihua Du, Vladimir N Uversky
Protein intrinsic disorder is an important characteristic commonly detected in multifunctional or RNA- and DNA-binding proteins. Due to their high conformational flexibility and solvent accessibility, intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) execute diverse functions including interaction with multiple partners, and are frequently subjected to various post-translational modifications. Recent studies on the components comprising the CRISPR (clustered regularly interspaced short palindromic repeats) system have elucidated the crystal structure of Cas9 proteins and the mechanism by which the Cas9-sgRNA complex recognizes and cleaves its target DNA...
July 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28689605/circadian-disruptions-in-the-myshkin-mouse-model-of-mania-are-independent-of-deficits-in-suprachiasmatic-molecular-clock-function
#18
Joseph W S Timothy, Natasza Klas, Harshmeena R Sanghani, Taghreed Al-Mansouri, Alun T L Hughes, Greer S Kirshenbaum, Vincent Brienza, Mino D C Belle, Martin R Ralph, Steven J Clapcote, Hugh D Piggins
BACKGROUND: Alterations in environmental light and intrinsic circadian function have strong associations with mood disorders. The neural origins underpinning these changes remain unclear, although genetic deficits in the molecular clock regularly render mice with altered mood-associated phenotypes. METHODS: A detailed circadian and light-associated behavioral characterization of the Na(+)/K(+)-ATPase α3 Myshkin (Myk/+) mouse model of mania was performed. Na(+)/K(+)-ATPase α3 does not reside within the core circadian molecular clockwork, but Myk/+ mice exhibit concomitant disruption in circadian rhythms and mood...
May 20, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28685932/usage-of-a-dataset-of-nmr-resolved-protein-structures-to-test-aggregation-vs-solubility-prediction-algorithms
#19
Daniel B Roche, Etienne Villain, Andrey V Kajava
There has been an increased interest in computational methods for amyloid and (or) aggregate prediction, due to the prevalence of these aggregates in numerous diseases and their recently discovered functional importance. To evaluate these methods, several datasets have been compiled. Typically, aggregation-prone regions of proteins, which form aggregates or amyloids in vivo, are more than 15 residues long and intrinsically disordered. However, the number of such experimentally established amyloid forming and non-forming sequences are limited, not exceeding one hundred entries in existing databases...
July 7, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28685247/vitiligo-focus-on-clinical-aspects-immunopathogenesis-and-therapy
#20
REVIEW
Katia Boniface, Julien Seneschal, Mauro Picardo, Alain Taïeb
Vitiligo is an acquired chronic depigmenting disorder of the skin, with an estimated prevalence of 0.5% of the general population, characterized by the development of white macules resulting from a loss of epidermal melanocytes. The nomenclature has been revised after an extensive international work within the vitiligo global issues consensus conference, and vitiligo (formerly non-segmental vitiligo) is now a consensus umbrella term for all forms of generalized vitiligo. Two other subsets of vitiligo are segmental vitiligo and unclassified/undetermined vitiligo, which corresponds to focal disease and rare variants...
July 6, 2017: Clinical Reviews in Allergy & Immunology
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