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Peter Tompa

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https://www.readbyqxmd.com/read/27899601/disprot-7-0-a-major-update-of-the-database-of-disordered-proteins
#1
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/27879390/phosphorylation-of-map65-1-by-arabidopsis-aurora-kinases-is-required-for-efficient-cell-cycle-progression
#2
Joanna Boruc, Annika Weimer, Virginie Stoppin-Mellet, Evelien Mylle, Ken Kosetsu, Cesyen Cedeno, Michel Jaquinod, Maria Njo, Liesbeth De Milde, Peter Tompa, Nathalie Gonzalez, Dirk Inze, Tom Beeckman, Marylin Vantard, Daniel van Damme
Aurora kinases are key effectors of mitosis. Plant Auroras are functionally divided into two clades. The α Auroras (Aurora1 and Aurora2) associate with the spindle and the cell plate and are implicated in controlling formative divisions throughout plant development. The β Aurora (Aurora3) localizes to centromeres and likely functions in chromosome separation. In contrast to the wealth of data available on the role of Aurora in other kingdoms, knowledge on their function in plants is merely emerging. This is exemplified by the fact that only histone H3 and the plant homologue of TPX2 have been identified as Aurora substrates in plants...
November 22, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27647212/coding-regions-of-intrinsic-disorder-accommodate-parallel-functions
#3
Rita Pancsa, Peter Tompa
Numerous DNA- and RNA-level functions are embedded in protein-coding regions, which constrains their structure, function, and evolution. Accumulating evidence suggests that such additional, overlapping functions occur preferentially in the coding sequences of intrinsically disordered proteins/regions (IDPs/IDRs), especially in those that are newly incorporated and thus have reduced selective pressure. It is the lack of strict structural constraints that makes disordered proteins more tolerant to mutations and thus more permissive to the appearance of overlapping functions within their coding sequences than structured domains...
September 16, 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27608806/essential-functions-linked-with-structural-disorder-in-organisms-of-minimal-genome
#4
Rita Pancsa, Peter Tompa
UNLABELLED: Intrinsically disordered regions (IDRs) of proteins fulfill important regulatory roles in most organisms. However, the proteins of certain endosymbiont and intracellular pathogenic bacteria with extremely reduced genomes contain disproportionately small amounts of IDRs, consisting almost entirely of folded domains. As their genomes co-evolving with their hosts have been reduced in unrelated lineages, the proteomes of these bacteria represent independently evolved minimal protein sets...
2016: Biology Direct
https://www.readbyqxmd.com/read/27569462/-influence-of-non-alcoholic-fatty-liver-disease-on-geno-and-immunotoxic-alterations-of-peripheric-blood-lymphocytes-of-oil-refinery-workers
#5
Anna Tompa, Anna Biró, Péter Balázs, Mátyás Jakab
INTRODUCTION: More than half of the Hungarian population is overweight or obese, therefore, non-alcoholic fatty liver is a common problem. According to clinical experience, 20-30% of fatty liver cases is not related to alcohol, but can be linked to diabetes, obesity or metabolic syndrome. AIM: The authors studied the correlation between genotoxicity, immuntoxicity and non-alcoholic fatty liver among oil refinery workers. METHOD: During this genotoxicological monitoring study the data of 107 exposed were compared to 67 controls...
August 2016: Orvosi Hetilap
https://www.readbyqxmd.com/read/27564234/a-novel-method-for-assessing-the-chaperone-activity-of-proteins
#6
Nevena Hristozova, Peter Tompa, Denes Kovacs
Protein chaperones are molecular machines which function both during homeostasis and stress conditions in all living organisms. Depending on their specific function, molecular chaperones are involved in a plethora of cellular processes by playing key roles in nascent protein chain folding, transport and quality control. Among stress protein families-molecules expressed during adverse conditions, infection, and diseases-chaperones are highly abundant. Their molecular functions range from stabilizing stress-susceptible molecules and membranes to assisting the refolding of stress-damaged proteins, thereby acting as protective barriers against cellular damage...
2016: PloS One
https://www.readbyqxmd.com/read/27561673/computational-analysis-of-translational-readthrough-proteins-in-drosophila-and-yeast-reveals-parallels-to-alternative-splicing
#7
Rita Pancsa, Mauricio Macossay-Castillo, Simone Kosol, Peter Tompa
In translational readthrough (TR) the ribosome continues extending the nascent protein beyond the first in-frame termination codon. Due to the lack of dedicated analyses of eukaryotic TR cases, the associated functional-evolutionary advantages are still unclear. Here, based on a variety of computational methods, we describe the structural and functional properties of previously proposed D. melanogaster and S. cerevisiae TR proteins and extensions. We found that in D. melanogaster TR affects long proteins in mainly regulatory roles...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27479031/molecular-mechanism-of-ssr128129e-an-extracellularly-acting-small-molecule-allosteric-inhibitor-of-fgf-receptor-signaling
#8
Corentin Herbert, Ulrich Schieborr, Krishna Saxena, Jarek Juraszek, Frederik De Smet, Chantal Alcouffe, Marc Bianciotto, Giorgio Saladino, David Sibrac, Denis Kudlinzki, Sridhar Sreeramulu, Alan Brown, Patrice Rigon, Jean-Pascal Herault, Gilbert Lassalle, Tom L Blundell, Frederic Rousseau, Ann Gils, Joost Schymkowitz, Peter Tompa, Jean-Marc Herbert, Peter Carmeliet, Francesco Luigi Gervasio, Harald Schwalbe, Françoise Bono
No abstract text is available yet for this article.
July 11, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27458588/editorial-function-and-flexibility-friend-or-foe
#9
Kris Pauwels, Peter Tompa
No abstract text is available yet for this article.
2016: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/27418282/wide-line-nmr-and-dsc-studies-on-intrinsically-disordered-p53-transactivation-domain-and-its-helically-pre-structured-segment
#10
Peter Tompa, Kyou-Hoon Han, Mónika Bokor, Pawel Kamasa, Ágnes Tantos, Beáta Fritz, Do-Hyoung Kim, Chewook Lee, Tamás Verebélyi, Kálmán Tompa
Wide-line 1H NMR intensity and differential scanning calorimetry measurements were carried out on the intrinsically disordered 73-residue full transactivation domain (TAD) of the p53 tumor suppressor protein and two peptides: one a wild type p53 TAD peptide with a helix pre-structuring property, and a mutant peptide with a disabled helix-forming propensity. Measurements were carried out in order to characterize their water and ion binding characteristics. By quantifying the number of hydrate water molecules, we provide a microscopic description for the interactions of water with a wild-type p53 TAD and two p53 TAD peptides...
September 2016: BMB Reports
https://www.readbyqxmd.com/read/27385826/numerous-proteins-with-unique-characteristics-are-degraded-by-the-26s-proteasome-following-monoubiquitination
#11
Ori Braten, Ido Livneh, Tamar Ziv, Arie Admon, Izhak Kehat, Lilac H Caspi, Hedva Gonen, Beatrice Bercovich, Adam Godzik, Samad Jahandideh, Lukasz Jaroszewski, Thomas Sommer, Yong Tae Kwon, Mainak Guharoy, Peter Tompa, Aaron Ciechanover
The "canonical" proteasomal degradation signal is a substrate-anchored polyubiquitin chain. However, a handful of proteins were shown to be targeted following monoubiquitination. In this study, we established-in both human and yeast cells-a systematic approach for the identification of monoubiquitination-dependent proteasomal substrates. The cellular wild-type polymerizable ubiquitin was replaced with ubiquitin that cannot form chains. Using proteomic analysis, we screened for substrates that are nevertheless degraded under these conditions compared with those that are stabilized, and therefore require polyubiquitination for their degradation...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27356874/intrinsic-protein-disorder-in-histone-lysine-methylation
#12
Tamas Lazar, Eva Schad, Beata Szabo, Tamas Horvath, Attila Meszaros, Peter Tompa, Agnes Tantos
UNLABELLED: Histone lysine methyltransferases (HKMTs), catalyze mono-, di- and trimethylation of lysine residues, resulting in a regulatory pattern that controls gene expression. Their involvement in many different cellular processes and diseases makes HKMTs an intensively studied protein group, but scientific interest so far has been concentrated mostly on their catalytic domains. In this work we set out to analyze the structural heterogeneity of human HKMTs and found that many contain long intrinsically disordered regions (IDRs) that are conserved through vertebrate species...
2016: Biology Direct
https://www.readbyqxmd.com/read/27242242/the-principle-of-conformational-signaling
#13
REVIEW
Peter Tompa
Signal transduction is the primary process by which cells respond to changes in their physical and chemical environments. Cellular response is initiated through a signaling protein (a receptor), which interacts with the "signal", most often a novel molecule outside or inside the cell. The mechanism of activation of the receptor is a conformational change and/or covalent modification, which then sets in motion a signaling pathway, i.e. a cascade of modification and binding events that relay and amplify the message to eventually alter the state of the cell...
July 25, 2016: Chemical Society Reviews
https://www.readbyqxmd.com/read/26941008/three-reasons-protein-disorder-analysis-makes-more-sense-in-the-light-of-collagen
#14
Ben Smithers, Matt E Oates, Peter Tompa, Julian Gough
We have identified that the collagen helix has the potential to be disruptive to analyses of intrinsically disordered proteins. The collagen helix is an extended fibrous structure that is both promiscuous and repetitive. Whilst its sequence is predicted to be disordered, this type of protein structure is not typically considered as intrinsic disorder. Here, we show that collagen-encoding proteins skew the distribution of exon lengths in genes. We find that previous results, demonstrating that exons encoding disordered regions are more likely to be symmetric, are due to the abundance of the collagen helix...
May 2016: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/26851277/design-principles-involving-protein-disorder-facilitate-specific-substrate-selection-and-degradation-by-the-ubiquitin-proteasome-system
#15
REVIEW
Mainak Guharoy, Pallab Bhowmick, Peter Tompa
The ubiquitin-proteasome system (UPS) regulates diverse cellular pathways by the timely removal (or processing) of proteins. Here we review the role of structural disorder and conformational flexibility in the different aspects of degradation. First, we discuss post-translational modifications within disordered regions that regulate E3 ligase localization, conformation, and enzymatic activity, and also the role of flexible linkers in mediating ubiquitin transfer and reaction processivity. Next we review well studied substrates and discuss that substrate elements (degrons) recognized by E3 ligases are highly disordered: short linear motifs recognized by many E3s constitute an important class of degrons, and these are almost always present in disordered regions...
March 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26789760/just-a-flexible-linker-the-structural-and-dynamic-properties-of-cbp-id4-revealed-by-nmr-spectroscopy
#16
Alessandro Piai, Eduardo O Calçada, Thomas Tarenzi, Alessandro Del Grande, Mihaly Varadi, Peter Tompa, Isabella C Felli, Roberta Pierattelli
Here, we present a structural and dynamic description of CBP-ID4 at atomic resolution. ID4 is the fourth intrinsically disordered linker of CREB-binding protein (CBP). In spite of the largely disordered nature of CBP-ID4, NMR chemical shifts and relaxation measurements show a significant degree of α-helix sampling in the protein regions encompassing residues 2-25 and 101-128 (1852-1875 and 1951-1978 in full-length CBP). Proline residues are uniformly distributed along the polypeptide, except for the two α-helical regions, indicating that they play an active role in modulating the structural features of this CBP fragment...
January 19, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/26582925/start2fold-a-database-of-hydrogen-deuterium-exchange-data-on-protein-folding-and-stability
#17
Rita Pancsa, Mihaly Varadi, Peter Tompa, Wim F Vranken
Proteins fulfil a wide range of tasks in cells; understanding how they fold into complex three-dimensional (3D) structures and how these structures remain stable while retaining sufficient dynamics for functionality is essential for the interpretation of overall protein behaviour. Since the 1950's, solvent exchange-based methods have been the most powerful experimental means to obtain information on the folding and stability of proteins. Considerable expertise and care were required to obtain the resulting datasets, which, despite their importance and intrinsic value, have never been collected, curated and classified...
January 4, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/26541461/redefining-the-bh3-death-domain-as-a-short-linear-motif
#18
REVIEW
Abdel Aouacheria, Christophe Combet, Peter Tompa, J Marie Hardwick
B cell lymphoma-2 (BCL-2)-related proteins control programmed cell death through a complex network of protein-protein interactions mediated by BCL-2 homology 3 (BH3) domains. Given their roles as dynamic linchpins, the discovery of novel BH3-containing proteins has attracted considerable attention. However, without a clearly defined BH3 signature sequence the BCL-2 family has expanded to include a nebulous group of nonhomologous BH3-only proteins, now justified by an intriguing twist. We present evidence that BH3s from both ordered and disordered proteins represent a new class of short linear motifs (SLiMs) or molecular recognition features (MoRFs) and are diverse in their evolutionary histories...
December 2015: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/26439842/functional-advantages-of-conserved-intrinsic-disorder-in-rna-binding-proteins
#19
Mihaly Varadi, Fruzsina Zsolyomi, Mainak Guharoy, Peter Tompa
Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains. We addressed their functionality through a quantitative description of the evolutionary conservation of disordered segments involved in binding, and investigated the structural implications of flexibility in terms of conformational stability and interface formation...
2015: PloS One
https://www.readbyqxmd.com/read/26437245/ensemble-methods-enable-a-new-definition-for-the-solution-to-gas-phase-transfer-of-intrinsically-disordered-proteins
#20
Antoni J Borysik, Denes Kovacs, Mainak Guharoy, Peter Tompa
Intrinsically disordered proteins (IDPs) are important for health and disease, yet their lack of net structure precludes an understanding of their function using classical methods. Gas-phase techniques provide a promising alternative to access information on the structure and dynamics of IDPs, but the fidelity to which these methods reflect the solution conformations of these proteins has been difficult to ascertain. Here we use state of the art ensemble techniques to investigate the solution to gas-phase transfer of a range of different IDPs...
November 4, 2015: Journal of the American Chemical Society
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