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Peter Tompa

Sara Contreras-Martos, Alessandro Piai, Simone Kosol, Mihaly Varadi, Angela Bekesi, Pierre Lebrun, Alexander N Volkov, Kris Gevaert, Roberta Pierattelli, Isabella C Felli, Peter Tompa
The multi-domain transcriptional coactivators CBP/p300 integrate a multitude of signaling inputs, interacting with more than 400 proteins via one or more of their globular domains. While CBP/p300 function is typically considered in terms of these structured domains, about half of the protein consists of intrinsically disordered regions (IDRs) of varying length. However, these IDRs have only been thought of as linkers that allow flexible spatial arrangement of the structured domains, but recent studies have shown that similar IDRs mediate specific and critical interactions in other proteins...
July 5, 2017: Scientific Reports
Kris Pauwels, Pierre Lebrun, Peter Tompa
There is ample evidence that many proteins or regions of proteins lack a well-defined folded structure under native-like conditions. These are called intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs). Whether this intrinsic disorder is also their main structural characteristic in living cells has been a matter of intense debate. The structural analysis of IDPs became an important challenge also because of their involvement in a plethora of human diseases, which made IDPs attractive targets for therapeutic development...
September 2017: Cellular and Molecular Life Sciences: CMLS
Cesyen Cedeño, Kris Pauwels, Peter Tompa
Understanding the biologically relevant structural and functional behavior of proteins inside living plant cells is only possible through the combination of structural biology and cell biology. The state-of-the-art structural biology techniques are typically applied to molecules that are isolated from their native context. Although most experimental conditions can be easily controlled while dealing with an isolated, purified protein, a serious shortcoming of such in vitro work is that we cannot mimic the extremely complex intracellular environment in which the protein exists and functions...
2017: Frontiers in Plant Science
Pietro Sormanni, Damiano Piovesan, Gabriella T Heller, Massimiliano Bonomi, Predrag Kukic, Carlo Camilloni, Monika Fuxreiter, Zsuzsanna Dosztanyi, Rohit V Pappu, M Madan Babu, Sonia Longhi, Peter Tompa, A Keith Dunker, Vladimir N Uversky, Silvio C E Tosatto, Michele Vendruscolo
No abstract text is available yet for this article.
March 22, 2017: Nature Chemical Biology
Hung Huy Nguyen, Mihaly Varadi, Peter Tompa, Kris Pauwels
Calpains are calcium-activated proteases that have biomedical and biotechnological potential. Their activity is tightly regulated by their endogenous inhibitor, calpastatin that binds to the enzyme only in the presence of calcium. Conventional approaches to purify calpain comprise multiple chromatographic steps, and are labor-intensive, leading to low yields. Here we report a new purification procedure for the human m-calpain based on its reversible calcium-mediated interaction with the intrinsically disordered calpastatin...
2017: PloS One
Steven Boeynaems, Elke Bogaert, Denes Kovacs, Albert Konijnenberg, Evy Timmerman, Alex Volkov, Mainak Guharoy, Mathias De Decker, Tom Jaspers, Veronica H Ryan, Abigail M Janke, Pieter Baatsen, Thomas Vercruysse, Regina-Maria Kolaitis, Dirk Daelemans, J Paul Taylor, Nancy Kedersha, Paul Anderson, Francis Impens, Frank Sobott, Joost Schymkowitz, Frederic Rousseau, Nicolas L Fawzi, Wim Robberecht, Philip Van Damme, Peter Tompa, Ludo Van Den Bosch
Liquid-liquid phase separation (LLPS) of RNA-binding proteins plays an important role in the formation of multiple membrane-less organelles involved in RNA metabolism, including stress granules. Defects in stress granule homeostasis constitute a cornerstone of ALS/FTLD pathogenesis. Polar residues (tyrosine and glutamine) have been previously demonstrated to be critical for phase separation of ALS-linked stress granule proteins. We now identify an active role for arginine-rich domains in these phase separations...
March 16, 2017: Molecular Cell
Cesyen Cedeño, Szymon Żerko, Peter Tompa, Wiktor Koźmiński
Early response to dehydration 10 protein (ERD10) is an intrinsically disordered protein from Arabidopsis thaliana. The protein is upregulated during stress however its mechanism of action at atomic level is not well understood. In the present work multidimensional NMR methodologies are used in order to facilitate the process of chemical shift assignment. The information provided here supports further NMR spectroscopy experiments aimed at elucidation of ERD10 behaviour during molecular recognition events with other proteins...
March 8, 2017: Biomolecular NMR Assignments
Kálmán Tompa, Mónika Bokor, Dorina Ágner, Dávid Iván, Dénes Kovács, Tamás Verebélyi, Péter Tompa
In this work the groundwork is laid for characterizing the mobility of hydrogen-hydrogen pairs (proton-proton radial vectors) in proteins in the solid state that contain only residual water. In this novel approach, we introduce new ways of analyzing and interpreting data: 1) by representing hydrogen mobility (HM) and melting diagram (MD) data recorded by wide-line (1) H NMR spectroscopic analysis as a function of fundamental temperature (thermal excitation energy); 2) by suggesting a novel mode of interpretation of these parameters that sheds light on details of protein-water interactions, such as the exact amount of water molecules and the distribution of barrier potentials pertaining to their rotational and surface translational mobility; 3) by relying on directly determined physical observables...
January 8, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
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
No abstract text is available yet for this article.
January 4, 2017: Nucleic Acids Research
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: 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...
January 4, 2017: Nucleic Acids Research
Joanna Boruc, Annika K Weimer, Virginie Stoppin-Mellet, Evelien Mylle, Ken Kosetsu, Cesyen Cedeño, Michel Jaquinod, Maria Njo, Liesbeth De Milde, Peter Tompa, Nathalie Gonzalez, Dirk Inzé, Tom Beeckman, Marylin Vantard, Daniël Van Damme
Aurora kinases are key effectors of mitosis. Plant Auroras are functionally divided into two clades. The alpha Auroras (Aurora1 and Aurora2) associate with the spindle and the cell plate and are implicated in controlling formative divisions throughout plant development. The beta 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 homolog of TPX2 have been identified as Aurora substrates in plants...
January 2017: Plant Physiology
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...
November 2016: Trends in Biochemical Sciences
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
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
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
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
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
Kris Pauwels, Peter Tompa
No abstract text is available yet for this article.
2016: Frontiers in Molecular Biosciences
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
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
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