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Keith dunker

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...
November 28, 2016: Nucleic Acids Research
Ao Zhou, Meng Li, Bo He, Weixing Feng, Fei Huang, Bing Xu, A Keith Dunker, Curt Balch, Baiyan Li, Yunlong Liu, Yue Wang
BACKGROUND: Lipopolysaccharide (LPS) is a gram-negative bacterial antigen that triggers a series of cellular responses. LPS pre-conditioning was previously shown to improve the therapeutic efficacy of bone marrow stromal cells/bone-marrow derived mesenchymal stem cells (BMSCs) for repairing ischemic, injured tissue. RESULTS: In this study, we systematically evaluated the effects of LPS treatment on genome-wide splicing pattern changes in mouse BMSCs by comparing transcriptome sequencing data from control vs...
2016: BMC Genomics
Prakash Kulkarni, A Keith Dunker, Keith Weninger, John Orban
Prostate-associated gene 4 (PAGE4) is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein (IDP) that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun. c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction...
September 2016: Asian Journal of Andrology
Gerard Kian-Meng Goh, A Keith Dunker, Vladimir N Uversky
Computational analyses revealed correlations between the intrinsic disorder propensity of shell proteins and case fatality rates (CFRs) among Flaviviruses and within at least two Flavivirus species, such as tick-borne encephalitis virus (TBEV) and dengue virus (DENV). The shell proteins analyzed in this study are capsid (C) and membrane (PrM, Pr, and M) proteins. The highest correlations can be found when regression analyses were conducted using Pr (Flavivirus: r(2) = 0.78, p < 0.01) or M (Flavivirus: r(2) = 0...
May 24, 2016: Molecular BioSystems
Jing Yan, A Keith Dunker, Vladimir N Uversky, Lukasz Kurgan
Intrinsically disordered proteins and protein regions offer numerous advantages in the context of protein-protein interactions when compared to the structured proteins and domains. These advantages include ability to interact with multiple partners, to fold into different conformations when bound to different partners, and to undergo disorder-to-order transitions concomitant with their functional activity. Molecular recognition features (MoRFs) are widespread elements located in disordered regions that undergo disorder-to-order transition upon binding to their protein partners...
March 2016: Molecular BioSystems
A Keith Dunker, Christopher J Oldfield
From the 1970s to the present, regions of missing electron density in protein structures determined by X-ray diffraction and the characterization of the functions of these regions have suggested that not all protein regions depend on prior 3D structure to carry out function. Motivated by these observations, in early 1996 we began to use bioinformatics approaches to study these intrinsically disordered proteins (IDPs) and IDP regions. At just about the same time, several laboratory groups began to study a collection of IDPs and IDP regions using nuclear magnetic resonance...
2015: Advances in Experimental Medicine and Biology
Fei Huang, Christopher J Oldfield, Bin Xue, Wei-Lun Hsu, Jingwei Meng, Xiaowen Liu, Li Shen, Pedro Romero, Vladimir N Uversky, A Keith Dunker
No abstract text is available yet for this article.
2015: BMC Bioinformatics
Gerard Kian-Meng Goh, A Keith Dunker, Vladimir N Uversky
The underlying reasons for the differences in the virulence of various types of Ebola virus (EBOV) remain unknown. Comparison of the percentage of disorder (PID) in nucleocapsid proteins VP30 and NP reveals high correlation between nucleocapsid PIDs and the case-fatality rates of EBOV. The higher disorder of these proteins is likely to be needed for more efficient multiplication of virus copies via more efficient viral RNA transcription and more promiscuous protein binding potential. This is important for the more efficient assistance of nucleocapsid in viral particle budding and of the assembly and mobility of viral proteins across the host membrane and within the cytoplasm...
August 2015: Molecular BioSystems
Gerard Kian-Meng Goh, A Keith Dunker, Vladimir N Uversky
This study involves measurements of percentages of intrinsic disorder (PIDs) in the GAG protein shells of various retroviruses. Unique patterns of shell protein disorder can be seen especially when GAG proteins (matrix M, capsid C, and nucleocapsid N) of primate and non-primate retroviruses are compared. HIV-1 presents the most unique pattern of disorder distribution with generally high levels of disorder in all three proteins, while EIAV (PIDs:: 26, 29, 13) is diametrically different from HIV-1 (N C M PIDs: 39...
August 2015: Molecular BioSystems
Karl J Niklas, Sarah E Bondos, A Keith Dunker, Stuart A Newman
Models for genetic regulation and cell fate specification characteristically assume that gene regulatory networks (GRNs) are essentially deterministic and exhibit multiple stable states specifying alternative, but pre-figured cell fates. Mounting evidence shows, however, that most eukaryotic precursor RNAs undergo alternative splicing (AS) and that the majority of transcription factors contain intrinsically disordered protein (IDP) domains whose functionalities are context dependent as well as subject to post-translational modification (PTM)...
2015: Frontiers in Cell and Developmental Biology
Patrick T Dolan, Andrew P Roth, Bin Xue, Ren Sun, A Keith Dunker, Vladimir N Uversky, Douglas J LaCount
Viral proteins bind to numerous cellular and viral proteins throughout the infection cycle. However, the mechanisms by which viral proteins interact with such large numbers of factors remain unknown. Cellular proteins that interact with multiple, distinct partners often do so through short sequences known as molecular recognition features (MoRFs) embedded within intrinsically disordered regions (IDRs). In this study, we report the first evidence that MoRFs in viral proteins play a similar role in targeting the host cell...
February 2015: Protein Science: a Publication of the Protein Society
A Keith Dunker, Sarah E Bondos, Fei Huang, Christopher J Oldfield
Intrinsically disordered proteins (IDPs) and IDP regions lack stable tertiary structure yet carry out numerous biological functions, especially those associated with signaling, transcription regulation, DNA condensation, cell division, and cellular differentiation. Both post-translational modifications (PTMs) and alternative splicing (AS) expand the functional repertoire of IDPs. Here we propose that an "IDP-based developmental toolkit," which is comprised of IDP regions, PTMs, especially multiple PTMs, within these IDP regions, and AS events within segments of pre-mRNA that code for these same IDP regions, allows functional diversification and environmental responsiveness for molecules that direct the development of complex metazoans...
January 2015: Seminars in Cell & Developmental Biology
Vikas Pejaver, Wei-Lun Hsu, Fuxiao Xin, A Keith Dunker, Vladimir N Uversky, Predrag Radivojac
UNLABELLED: The structural, functional, and mechanistic characterization of several types of post-translational modifications (PTMs) is well-documented. PTMs, however, may interact or interfere with one another when regulating protein function. Yet, characterization of the structural and functional signatures of their crosstalk has been hindered by the scarcity of data. To this end, we developed a unified sequence-based predictor of 23 types of PTM sites that, we believe, is a useful tool in guiding biological experiments and data interpretation...
August 2014: Protein Science: a Publication of the Protein Society
Robin van der Lee, Marija Buljan, Benjamin Lang, Robert J Weatheritt, Gary W Daughdrill, A Keith Dunker, Monika Fuxreiter, Julian Gough, Joerg Gsponer, David T Jones, Philip M Kim, Richard W Kriwacki, Christopher J Oldfield, Rohit V Pappu, Peter Tompa, Vladimir N Uversky, Peter E Wright, M Madan Babu
No abstract text is available yet for this article.
July 9, 2014: Chemical Reviews
Christopher J Oldfield, A Keith Dunker
Intrinsically disordered proteins (IDPs) and IDP regions fail to form a stable structure, yet they exhibit biological activities. Their mobile flexibility and structural instability are encoded by their amino acid sequences. They recognize proteins, nucleic acids, and other types of partners; they accelerate interactions and chemical reactions between bound partners; and they help accommodate posttranslational modifications, alternative splicing, protein fusions, and insertions or deletions. Overall, IDP-associated biological activities complement those of structured proteins...
2014: Annual Review of Biochemistry
Jonah Kallenbach, Wei-Lun Hsu, A Keith Dunker, Gil Alterovitz
Signal transduction pathways are of critical importance in disease and regulation of cellular functions. Proteins that do not fold to a state of stable tertiary structure, known as intrinsically disordered proteins, are highly represented in signaling pathways and protein interaction networks. Important examples of disordered signaling proteins include p53 and BRCA1, and approximately 40% of Eukaryotic proteins are estimated to have significant disordered regions. Certain regions within these disordered proteins, however, can take on an ordered structure upon binding to a partner...
2013: AMIA Summits on Translational Science Proceedings
Gerard Kian-Meng Goh, A Keith Dunker, Vladimir Uversky
A novel coronavirus, MERS-CoV (NCoV, HCoV-EMC/2012), originating from the Middle-East, has been discovered. Incoming data reveal that the virus is highly virulent to humans. A model that categorizes coronaviuses according to the hardness of their shells was developed before the discovery of MERS-CoV. Using protein intrinsic disorder prediction, coronaviruses were categorized into three groups that can be linked to the levels of oral-fecal and respiratory transmission regardless of genetic proximity. Using this model, MERS-CoV is placed into disorder group C, which consists of coronaviruses that have relatively hard inner and outer shells...
2013: PLoS Currents
Mihaly Varadi, Simone Kosol, Pierre Lebrun, Erica Valentini, Martin Blackledge, A Keith Dunker, Isabella C Felli, Julie D Forman-Kay, Richard W Kriwacki, Roberta Pierattelli, Joel Sussman, Dmitri I Svergun, Vladimir N Uversky, Michele Vendruscolo, David Wishart, Peter E Wright, Peter Tompa
The goal of pE-DB ( is to serve as an openly accessible database for the deposition of structural ensembles of intrinsically disordered proteins (IDPs) and of denatured proteins based on nuclear magnetic resonance spectroscopy, small-angle X-ray scattering and other data measured in solution. Owing to the inherent flexibility of IDPs, solution techniques are particularly appropriate for characterizing their biophysical properties, and structural ensembles in agreement with these data provide a convenient tool for describing the underlying conformational sampling...
January 2014: Nucleic Acids Research
Zhenling Peng, Christopher J Oldfield, Bin Xue, Marcin J Mizianty, A Keith Dunker, Lukasz Kurgan, Vladimir N Uversky
Intrinsic disorder (i.e., lack of a unique 3-D structure) is a common phenomenon, and many biologically active proteins are disordered as a whole, or contain long disordered regions. These intrinsically disordered proteins/regions constitute a significant part of all proteomes, and their functional repertoire is complementary to functions of ordered proteins. In fact, intrinsic disorder represents an important driving force for many specific functions. An illustrative example of such disorder-centric functional class is RNA-binding proteins...
April 2014: Cellular and Molecular Life Sciences: CMLS
Poornima Bhat-Nakshatri, Eun-Kyung Song, Nikail R Collins, Vladimir N Uversky, A Keith Dunker, Bert W O'Malley, Tim R Geistlinger, Jason S Carroll, Myles Brown, Harikrishna Nakshatri
BACKGROUND: Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown. METHODS: MCF-7 and its anti-estrogen derivatives were used for the majority of the assays...
2013: BMC Medical Genomics
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