IDEAL in 2014 illustrates interaction networks composed of intrinsically disordered proteins and their binding partners

IDEAL (Intrinsically Disordered proteins with Extensive Annotations and Literature, http://www.ideal.force.cs.is.nagoya-u.ac.jp/IDEAL/) is a collection of intrinsically disordered proteins (IDPs) that cannot adopt stable globular structures under physiological conditions. Since its previous publication in 2012, the number of entries in IDEAL has almost tripled (120 to 340). In addition to the increase in quantity, the quality of IDEAL has been significantly improved. The new IDEAL incorporates the interactions of IDPs and their binding partners more explicitly, and illustrates the protein–protein interaction (PPI) networks and the structures of protein complexes. Redundant experimental data are arranged based on the clustering of Protein Data Bank entries, and similar sequences with the same binding mode are grouped. As a result, the new IDEAL presents more concise and informative experimental data. Nuclear magnetic resonance (NMR) disorder is annotated in a systematic manner, by identifying the regions with large deviations among the NMR models. The ordered/disordered and new domain predictions by DICHOT are available, as well as the domain assignments by HMMER. Some examples of the PPI networks and the highly deviated regions derived from NMR models will be described, together with other advances. These enhancements will facilitate deeper understanding of IDPs, in terms of their flexibility, plasticity and promiscuity.

[1]  María Martín,et al.  Activities at the Universal Protein Resource (UniProt) , 2013, Nucleic Acids Res..

[2]  J. S. Sodhi,et al.  Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. , 2004, Journal of molecular biology.

[3]  Richard J. Edwards,et al.  ELM—the database of eukaryotic linear motifs , 2011, Nucleic Acids Res..

[4]  H. Dyson,et al.  Intrinsically unstructured proteins and their functions , 2005, Nature Reviews Molecular Cell Biology.

[5]  Miron Livny,et al.  BioMagResBank , 2007, Nucleic Acids Res..

[6]  A. Shilatifard,et al.  Covalent modifications of histones during development and disease pathogenesis , 2007, Nature Structural &Molecular Biology.

[7]  L. Iakoucheva,et al.  Intrinsic disorder in cell-signaling and cancer-associated proteins. , 2002, Journal of molecular biology.

[8]  H. Dyson,et al.  Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. , 1999, Journal of molecular biology.

[9]  Michail Yu. Lobanov,et al.  ComSin: database of protein structures in bound (complex) and unbound (single) states in relation to their intrinsic disorder , 2009, Nucleic Acids Res..

[10]  B. Matthews.  Comparison of the predicted and observed secondary structure of T4 phage lysozyme. , 1975, Biochimica et biophysica acta.

[11]  R. Ozawa,et al.  A comprehensive two-hybrid analysis to explore the yeast protein interactome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[12]  V. Uversky,et al.  Why are “natively unfolded” proteins unstructured under physiologic conditions? , 2000, Proteins.

[13]  Haruki Nakamura,et al.  Disordered domains and high surface charge confer hubs with the ability to interact with multiple proteins in interaction networks , 2006, FEBS letters.

[14]  R. Lanz,et al.  Nuclear receptor coregulators: cellular and molecular biology. , 1999, Endocrine reviews.

[15]  P E Wright,et al.  Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates binding diversity. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  H. Jane Dyson,et al.  Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein , 2009, Proceedings of the National Academy of Sciences.

[17]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[18]  Johanna Witzell,et al.  Resistance to Dutch Elm Disease Reduces Presence of Xylem Endophytic Fungi in Elms (Ulmus spp.) , 2013, PloS one.

[19]  V. Uversky.  Intrinsically Disordered Proteins , 2014 .

[20]  David S. Goodsell,et al.  The RCSB Protein Data Bank: new resources for research and education , 2012, Nucleic Acids Res..

[21]  Robert D. Finn,et al.  HMMER web server: interactive sequence similarity searching , 2011, Nucleic Acids Res..

[22]  K. Nishikawa,et al.  Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation. , 2006, Journal of molecular biology.

[23]  István Simon,et al.  Preformed structural elements feature in partner recognition by intrinsically unstructured proteins. , 2004, Journal of molecular biology.

[24]  The UniProt Consortium,et al.  Update on activities at the Universal Protein Resource (UniProt) in 2013 , 2012, Nucleic Acids Res..

[25]  P. Tompa.  The interplay between structure and function in intrinsically unstructured proteins , 2005, FEBS letters.

[26]  James R. Knight,et al.  A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae , 2000, Nature.

[27]  A. Levine.  p53, the Cellular Gatekeeper for Growth and Division , 1997, Cell.

[28]  Marc S. Cortese,et al.  Analysis of molecular recognition features (MoRFs). , 2006, Journal of molecular biology.

[29]  A. Dunker,et al.  Understanding protein non-folding. , 2010, Biochimica et biophysica acta.

[30]  Motonori Ota,et al.  IDEAL: Intrinsically Disordered proteins with Extensive Annotations and Literature , 2011, Nucleic Acids Res..

[31]  G. Hong,et al.  Nucleic Acids Research , 2015, Nucleic Acids Research.

[32]  Zoran Obradovic,et al.  DisProt: the Database of Disordered Proteins , 2006, Nucleic Acids Res..

[33]  Lilia M. Iakoucheva,et al.  Intrinsic Disorder Is a Common Feature of Hub Proteins from Four Eukaryotic Interactomes , 2006, PLoS Comput. Biol..

[34]  A Keith Dunker,et al.  An assignment of intrinsically disordered regions of proteins based on NMR structures. , 2013, Journal of structural biology.

[35]  A Keith Dunker,et al.  Intrinsic disorder and protein function. , 2002, Biochemistry.

[36]  Hans Clevers,et al.  Wnt/β-Catenin Signaling and Disease , 2012, Cell.

[37]  Silvio C. E. Tosatto,et al.  MobiDB: a comprehensive database of intrinsic protein disorder annotations , 2012, Bioinform..

[38]  Lukasz A. Kurgan,et al.  D2P2: database of disordered protein predictions , 2012, Nucleic Acids Res..

[39]  Christopher J. Oldfield,et al.  Intrinsically disordered protein. , 2001, Journal of molecular graphics & modelling.

[40]  Bostjan Kobe,et al.  Structural Basis for the Specificity of Bipartite Nuclear Localization Sequence Binding by Importin-α* , 2003, Journal of Biological Chemistry.

[41]  David T. Jones,et al.  Prediction of disordered regions in proteins from position specific score matrices , 2003, Proteins.

[42]  Takashi Gojobori,et al.  Binary classification of protein molecules into intrinsically disordered and ordered segments , 2011, BMC Structural Biology.