Flexible nets

Proteins participate in complex sets of interactions that represent the mechanistic foundation for much of the physiology and function of the cell. These protein–protein interactions are organized into exquisitely complex networks. The architecture of protein–protein interaction networks was recently proposed to be scale‐free, with most of the proteins having only one or two connections but with relatively fewer ‘hubs’ possessing tens, hundreds or more links. The high level of hub connectivity must somehow be reflected in protein structure. What structural quality of hub proteins enables them to interact with large numbers of diverse targets? One possibility would be to employ binding regions that have the ability to bind multiple, structurally diverse partners. This trait can be imparted by the incorporation of intrinsic disorder in one or both partners. To illustrate the value of such contributions, this review examines the roles of intrinsic disorder in protein network architecture. We show that there are three general ways that intrinsic disorder can contribute: First, intrinsic disorder can serve as the structural basis for hub protein promiscuity; secondly, intrinsically disordered proteins can bind to structured hub proteins; and thirdly, intrinsic disorder can provide flexible linkers between functional domains with the linkers enabling mechanisms that facilitate binding diversity. An important research direction will be to determine what fraction of protein–protein interaction in regulatory networks relies on intrinsic disorder.

[1]  E. Fischer Einfluss der Configuration auf die Wirkung der Enzyme , 1894 .

[2]  J. Barsoum,et al.  Cellular and SV40 chromatin: replication, segregation, ubiquitination, nuclease-hypersensitive sites, HMG-containing nucleosomes, and heterochromatin-specific protein. , 1983, Cold Spring Harbor symposia on quantitative biology.

[3]  S. Laland,et al.  On the presence of two new high mobility group‐like proteins in HeLa S3 cells , 1983, FEBS letters.

[4]  A. Bretscher,et al.  Smooth muscle caldesmon is an extended flexible monomeric protein in solution that can readily undergo reversible intra- and intermolecular sulfhydryl cross-linking. A mechanism for caldesmon's F-actin bundling activity. , 1987, The Journal of biological chemistry.

[5]  C. Bugg,et al.  Structure of calmodulin refined at 2.2 A resolution. , 1988, Journal of molecular biology.

[6]  K. Hiwada,et al.  Vascular Smooth Muscle Calponin: A Novel Troponin T‐like Protein , 1988, Hypertension.

[7]  P. Sigler,et al.  Acid blobs and negative noodles , 1988, Nature.

[8]  R. Reeves,et al.  High-mobility group protein HMG-I localizes to G/Q- and C-bands of human and mouse chromosomes , 1989, The Journal of cell biology.

[9]  M. Nissen,et al.  The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. , 1990, The Journal of biological chemistry.

[10]  J. Woodgett,et al.  Glycogen synthase kinase-3: functions in oncogenesis and development. , 1992, Biochimica et biophysica acta.

[11]  R. Reeves Chromatin changes during the cell cycle. , 1992, Current opinion in cell biology.

[12]  K. Tanaka,et al.  Mutational analysis of the structure and function of the xeroderma pigmentosum group A complementing protein. Identification of essential domains for nuclear localization and DNA excision repair. , 1992, The Journal of biological chemistry.

[13]  M Ikura,et al.  Backbone dynamics of calmodulin studied by 15N relaxation using inverse detected two-dimensional NMR spectroscopy: the central helix is flexible. , 1992, Biochemistry.

[14]  S. Elledge,et al.  The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases , 1993, Cell.

[15]  R. Wood,et al.  Preferential binding of the xeroderma pigmentosum group A complementing protein to damaged DNA. , 1993, Biochemistry.

[16]  M. Nissen,et al.  Interaction of high mobility group-I (Y) nonhistone proteins with nucleosome core particles. , 1993, The Journal of biological chemistry.

[17]  C. Schutt,et al.  The structure of crystalline profilin–β-actin , 1993, Nature.

[18]  S. Elledge,et al.  Specific association between the human DNA repair proteins XPA and ERCC1. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[19]  James M. Roberts,et al.  Cloning of p27 Kip1 , a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals , 1994, Cell.

[20]  K. Tanaka,et al.  The XPA protein is a zinc metalloprotein with an ability to recognize various kinds of DNA damage. , 1994, Mutation research.

[21]  R Grosschedl,et al.  HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. , 1994, Trends in genetics : TIG.

[22]  Tony Hunter,et al.  p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21 , 1994, Cell.

[23]  R. S. Spolar,et al.  Coupling of local folding to site-specific binding of proteins to DNA. , 1994, Science.

[24]  P. Cohen,et al.  Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B , 1995, Nature.

[25]  M. Nissen,et al.  1H and 13C NMR assignments and molecular modelling of a minor groove DNA-binding peptide from the HMG-I protein. , 2009, International journal of peptide and protein research.

[26]  A. Sancar,et al.  The General Transcription-Repair Factor TFIIH Is Recruited to the Excision Repair Complex by the XPA Protein Independent of the TFIIE Transcription Factor (*) , 1995, The Journal of Biological Chemistry.

[27]  S. Elledge,et al.  p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. , 1995, Genes & development.

[28]  S. Elledge,et al.  Inhibition of cyclin-dependent kinases by p21. , 1995, Molecular biology of the cell.

[29]  R. Legerski,et al.  An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair , 1995, Molecular and cellular biology.

[30]  R. Wood,et al.  Enhancement of damage-specific DNA binding of XPA by interaction with the ERCC1 DNA repair protein. , 1995, Biochemical and biophysical research communications.

[31]  Y. Sung,et al.  Transactivation Ability of p53 Transcriptional Activation Domain Is Directly Related to the Binding Affinity to TATA-binding Protein (*) , 1995, The Journal of Biological Chemistry.

[32]  David O. Morgan,et al.  Principles of CDK regulation , 1995, Nature.

[33]  Anna Tempczyk,et al.  Crystal structures of human calcineurin and the human FKBP12–FK506–calcineurin complex , 1995, Nature.

[34]  A. Levine,et al.  Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain , 1996, Science.

[35]  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.

[36]  K. Tanaka,et al.  Sequential binding of DNA repair proteins RPA and ERCC1 to XPA in vitro. , 1996, Nucleic acids research.

[37]  A. Simeone,et al.  High level expression of the HMGI (Y) gene during embryonic development. , 1996, Oncogene.

[38]  R. Reeves,et al.  High-mobility-group chromosomal proteins: architectural components that facilitate chromatin function. , 1996, Progress in nucleic acid research and molecular biology.

[39]  P. Roche,et al.  Identification of a Novel Syntaxin- and Synaptobrevin/VAMP-binding Protein, SNAP-23, Expressed in Non-neuronal Tissues* , 1996, The Journal of Biological Chemistry.

[40]  K. Tanaka,et al.  Identification of a damaged-DNA binding domain of the XPA protein. , 1996, Mutation research.

[41]  P. Lansbury,et al.  NACP, a protein implicated in Alzheimer's disease and learning, is natively unfolded. , 1996, Biochemistry.

[42]  Philip D. Jeffrey,et al.  Crystal structure of the p27Kip1 cyclin-dependent-kinase inibitor bound to the cyclin A–Cdk2 complex , 1996, Nature.

[43]  A T Brünger,et al.  Structural Changes Are Associated with Soluble N-Ethylmaleimide-sensitive Fusion Protein Attachment Protein Receptor Complex Formation* , 1997, The Journal of Biological Chemistry.

[44]  J. Egly,et al.  DNA Damage Recognition by XPA Protein Promotes Efficient Recruitment of Transcription Factor II H* , 1997, The Journal of Biological Chemistry.

[45]  A. Rhoads,et al.  Sequence motifs for calmodulin recognition , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[46]  D O Morgan,et al.  Cyclin-dependent kinases: engines, clocks, and microprocessors. , 1997, Annual review of cell and developmental biology.

[47]  V. De Filippis,et al.  Probing the partly folded states of proteins by limited proteolysis. , 1997, Folding & design.

[48]  J. Cleaver,et al.  The DNA damage-recognition problem in human and other eukaryotic cells: the XPA damage binding protein. , 1997, The Biochemical journal.

[49]  Jeffrey R. Huth,et al.  The solution structure of an HMG-I(Y)–DNA complex defines a new architectural minor groove binding motif , 1997, Nature Structural Biology.

[50]  A.K. Dunker,et al.  Identifying disordered regions in proteins from amino acid sequence , 1997, Proceedings of International Conference on Neural Networks (ICNN'97).

[51]  W. Annaert,et al.  Export of Cellubrevin from the Endoplasmic Reticulum Is Controlled by BAP31 , 1997, The Journal of cell biology.

[52]  N. Gusev,et al.  Interaction of isoforms of S100 protein with smooth muscle caldesmon , 1998, FEBS letters.

[53]  T. Ikegami,et al.  Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA , 1998, Nature Structural &Molecular Biology.

[54]  A. Klip,et al.  Identification of a human homologue of the vesicle-associated membrane protein (VAMP)-associated protein of 33 kDa (VAP-33): a broadly expressed protein that binds to VAMP. , 1998, The Biochemical journal.

[55]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[56]  H. Youn,et al.  Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes. , 1998, Immunity.

[57]  A. Sparks,et al.  Identification of c-MYC as a target of the APC pathway. , 1998, Science.

[58]  G. W. Buchko,et al.  Structural features of the minimal DNA binding domain (M98-F219) of human nucleotide excision repair protein XPA. , 1998, Nucleic acids research.

[59]  G. Marius Clore,et al.  Improving the Packing and Accuracy of NMR Structures with a Pseudopotential for the Radius of Gyration , 1999 .

[60]  Y. Nishimura,et al.  Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins. , 1999, Biochemical and biophysical research communications.

[61]  P. Cohen,et al.  The Croonian Lecture 1998. Identification of a protein kinase cascade of major importance in insulin signal transduction. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[62]  M. Nissen,et al.  Purification and assays for high mobility group HMG-I(Y) protein function. , 1999, Methods in enzymology.

[63]  Raymond L. White,et al.  Regulation of β-Catenin Signaling by the B56 Subunit of Protein Phosphatase 2A , 1999 .

[64]  Heinz Ruffner,et al.  BRCA1 Is Phosphorylated at Serine 1497 In Vivo at a Cyclin-Dependent Kinase 2 Phosphorylation Site , 1999, Molecular and Cellular Biology.

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

[66]  O. MacDougald,et al.  Glycogen Synthase Kinase 3 Is an Insulin-Regulated C/EBPα Kinase , 1999, Molecular and Cellular Biology.

[67]  F. Costantini,et al.  Identification of a Domain of Axin That Binds to the Serine/Threonine Protein Phosphatase 2A and a Self-binding Domain* , 1999, The Journal of Biological Chemistry.

[68]  N. Pavletich Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. , 1999, Journal of molecular biology.

[69]  M. Erdos,et al.  BRCA1 inhibition of estrogen receptor signaling in transfected cells. , 1999, Science.

[70]  Albert,et al.  Emergence of scaling in random networks , 1999, Science.

[71]  J. Hopfield,et al.  From molecular to modular cell biology , 1999, Nature.

[72]  M. Yaffe,et al.  Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding. , 1999, Molecular cell.

[73]  J. Hoeijmakers,et al.  XAB2, a Novel Tetratricopeptide Repeat Protein Involved in Transcription-coupled DNA Repair and Transcription* , 2000, The Journal of Biological Chemistry.

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

[75]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[76]  V. Uversky Intrinsically Disordered Proteins , 2000 .

[77]  J. Hoeijmakers,et al.  Nucleotide excision repair and human syndromes. , 2000, Carcinogenesis.

[78]  G. Liu,et al.  Estrogen receptor protects p53 from deactivation by human double minute-2. , 2000, Cancer research.

[79]  P. Polakis Wnt signaling and cancer. , 2000, Genes & development.

[80]  Albert-László Barabási,et al.  Error and attack tolerance of complex networks , 2000, Nature.

[81]  E. Olson,et al.  Calsarcins, a novel family of sarcomeric calcineurin-binding proteins. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[82]  S. Masters,et al.  14-3-3 proteins: structure, function, and regulation. , 2000, Annual review of pharmacology and toxicology.

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

[84]  R. Albert,et al.  The large-scale organization of metabolic networks , 2000, Nature.

[85]  K. Tanaka,et al.  A novel cytoplasmic GTPase XAB1 interacts with DNA repair protein XPA. , 2000, Nucleic acids research.

[86]  Paul J. McLaughlin,et al.  Latrunculin alters the actin-monomer subunit interface to prevent polymerization , 2000, Nature Cell Biology.

[87]  Richard D. Smith,et al.  Identification of intrinsic order and disorder in the DNA repair protein XPA , 2001, Protein science : a publication of the Protein Society.

[88]  Albert-László Barabási,et al.  The physics of the Web , 2001 .

[89]  Ioannis Xenarios,et al.  DIP: The Database of Interacting Proteins: 2001 update , 2001, Nucleic Acids Res..

[90]  A. Demchenko,et al.  Recognition between flexible protein molecules: induced and assisted folding † , 2001, Journal of molecular recognition : JMR.

[91]  K. Lumb,et al.  Effects of macromolecular crowding on the intrinsically disordered proteins c-Fos and p27(Kip1). , 2001, Biomacromolecules.

[92]  P. Romero,et al.  Sequence complexity of disordered protein , 2001, Proteins.

[93]  Zoran Obradovic,et al.  The protein trinity—linking function and disorder , 2001, Nature Biotechnology.

[94]  A. Barabasi,et al.  Lethality and centrality in protein networks , 2001, Nature.

[95]  Erich A. Nigg,et al.  Cell division: Mitotic kinases as regulators of cell division and its checkpoints , 2001, Nature Reviews Molecular Cell Biology.

[96]  A. Reith,et al.  The Structure of Phosphorylated GSK-3β Complexed with a Peptide, FRATtide, that Inhibits β-Catenin Phosphorylation , 2001 .

[97]  R. Reeves,et al.  HMGI/Y proteins: flexible regulators of transcription and chromatin structure. , 2001, Biochimica et biophysica acta.

[98]  T. Härd,et al.  The N-terminal Regions of Estrogen Receptor α and β Are Unstructured in Vitro and Show Different TBP Binding Properties* , 2001, The Journal of Biological Chemistry.

[99]  Jeff Hasty,et al.  Protein interactions: Unspinning the web , 2001, Nature.

[100]  K. Namba Roles of partly unfolded conformations in macromolecular self‐assembly , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[101]  Laurence H. Pearl,et al.  Crystal Structure of Glycogen Synthase Kinase 3β Structural Basis for Phosphate-Primed Substrate Specificity and Autoinhibition , 2001, Cell.

[102]  K. Aktories,et al.  Interaction of ADP‐ribosylated actin with actin binding proteins , 2001, FEBS letters.

[103]  R. Reeves,et al.  Molecular biology of HMGA proteins: hubs of nuclear function. , 2001, Gene.

[104]  Gary D Bader,et al.  BIND--The Biomolecular Interaction Network Database. , 2001, Nucleic acids research.

[105]  B. Rost,et al.  Comparing function and structure between entire proteomes , 2001, Protein science : a publication of the Protein Society.

[106]  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.

[107]  A. Wagner The yeast protein interaction network evolves rapidly and contains few redundant duplicate genes. , 2001, Molecular biology and evolution.

[108]  R. Kriwacki,et al.  Defining the molecular basis of Arf and Hdm2 interactions. , 2001, Journal of molecular biology.

[109]  W. Deppert,et al.  Two Immunologically Distinct Human DNA Polymerase α-Primase Subpopulations Are Involved in Cellular DNA Replication , 2001, Molecular and Cellular Biology.

[110]  H. Dyson,et al.  Coupling of folding and binding for unstructured proteins. , 2002, Current opinion in structural biology.

[111]  J. Blasi,et al.  Munc 18a Binding to Syntaxin 1A and 1B Isoforms Defines Its Localization at the Plasma Membrane and Blocks SNARE Assembly in a Three-Hybrid System Assay , 2002, Molecular and Cellular Neuroscience.

[112]  V. Uversky Natively unfolded proteins: A point where biology waits for physics , 2002, Protein science : a publication of the Protein Society.

[113]  Calmodulin is a selective modulator of estrogen receptors. , 2002, Molecular endocrinology.

[114]  P. Tompa Intrinsically unstructured proteins. , 2002, Trends in biochemical sciences.

[115]  Vladimir N Uversky,et al.  What does it mean to be natively unfolded? , 2002, European journal of biochemistry.

[116]  Gary D Bader,et al.  Analyzing yeast protein–protein interaction data obtained from different sources , 2002, Nature Biotechnology.

[117]  Alexander S. Banks,et al.  Cutting Edge: Suppressor of Cytokine Signaling 3 Inhibits Activation of NFATp , 2002, The Journal of Immunology.

[118]  Ariel Fernández,et al.  Insufficiently dehydrated hydrogen bonds as determinants of protein interactions , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[119]  Benno Schwikowski,et al.  Discovering regulatory and signalling circuits in molecular interaction networks , 2002, ISMB.

[120]  Ariel Fernández,et al.  Three-body correlations in protein folding: the origin of cooperativity , 2002 .

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

[122]  B. Snel,et al.  Comparative assessment of large-scale data sets of protein–protein interactions , 2002, Nature.

[123]  L. Iakoucheva,et al.  Intrinsic Disorder and Protein Function , 2002 .

[124]  Hawoong Jeong,et al.  Classification of scale-free networks , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[125]  Z. Obradovic,et al.  Identification and functions of usefully disordered proteins. , 2002, Advances in protein chemistry.

[126]  Joshua N Adkins,et al.  Functional consequences of preorganized helical structure in the intrinsically disordered cell-cycle inhibitor p27(Kip1). , 2001, Biochemistry.

[127]  T. Dale,et al.  Wnt signal transduction: kinase cogs in a nano-machine? , 2002, Trends in biochemical sciences.

[128]  L. Serpell,et al.  Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor , 2002, The EMBO journal.

[129]  P. Tompa Intrinsically unstructured proteins evolve by repeat expansion , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[130]  V. Uversky,et al.  Protein folding revisited. A polypeptide chain at the folding – misfolding – nonfolding cross-roads: which way to go? , 2003, Cellular and Molecular Life Sciences CMLS.

[131]  A. Valencia,et al.  Protein interaction: same network, different hubs. , 2003, Trends in genetics : TIG.

[132]  Wen-Hsiung Li,et al.  Evolution of the yeast protein interaction network , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[133]  Ariel Fernández,et al.  Dehydron: a structurally encoded signal for protein interaction. , 2003, Biophysical journal.

[134]  James R. Knight,et al.  A Protein Interaction Map of Drosophila melanogaster , 2003, Science.

[135]  B. Sommer,et al.  Part I: Parkin-associated proteins and Parkinson’s disease , 2003, Neuropharmacology.

[136]  L. Pearl,et al.  Structural basis for recruitment of glycogen synthase kinase 3β to the axin—APC scaffold complex , 2003, The EMBO journal.

[137]  Ariel Fernández,et al.  Adherence of packing defects in soluble proteins. , 2003, Physical review letters.

[138]  R. Nussinov,et al.  Extended disordered proteins: targeting function with less scaffold. , 2003, Trends in biochemical sciences.

[139]  S. Vucetic,et al.  Flavors of protein disorder , 2003, Proteins.

[140]  César A. Hidalgo,et al.  Scale-free networks , 2008, Scholarpedia.

[141]  X. Estivill,et al.  Phosphorylation of calcipressin 1 increases its ability to inhibit calcineurin and decreases calcipressin half-life. , 2003, The Biochemical journal.

[142]  V. Buchman,et al.  Part II: α-synuclein and its molecular pathophysiological role in neurodegenerative disease , 2003, Neuropharmacology.

[143]  Guillermina Lozano,et al.  MDM2, an introduction. , 2003, Molecular cancer research : MCR.

[144]  S. Vetter,et al.  Novel aspects of calmodulin target recognition and activation. , 2003, European journal of biochemistry.

[145]  Zoran Obradovic,et al.  Predicting intrinsic disorder from amino acid sequence , 2003, Proteins.

[146]  Cheng-Yan Kao,et al.  POINT: a database for the prediction of protein-protein interactions based on the orthologous interactome , 2004, Bioinform..

[147]  Sui Huang,et al.  Back to the biology in systems biology: what can we learn from biomolecular networks? , 2004, Briefings in functional genomics & proteomics.

[148]  Ariel Fernández Functionality of wrapping defects in soluble proteins: what cannot be kept dry must be conserved. , 2004, Journal of molecular biology.

[149]  L. Hengst,et al.  p27 binds cyclin–CDK complexes through a sequential mechanism involving binding-induced protein folding , 2004, Nature Structural &Molecular Biology.

[150]  Carol V Robinson,et al.  Studies of the RNA degradosome-organizing domain of the Escherichia coli ribonuclease RNase E. , 2004, Journal of molecular biology.

[151]  Yoshio Miki,et al.  Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage , 2004, Cancer science.

[152]  Dipanwita Roy Chowdhury,et al.  Human protein reference database as a discovery resource for proteomics , 2004, Nucleic Acids Res..

[153]  Ariel Fernández,et al.  Molecular dimension explored in evolution to promote proteomic complexity. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[154]  Sonia Longhi,et al.  The C-terminal domain of measles virus nucleoprotein belongs to the class of intrinsically disordered proteins that fold upon binding to their physiological partner. , 2004, Virus research.

[155]  S. L. Wong,et al.  A Map of the Interactome Network of the Metazoan C. elegans , 2004, Science.

[156]  I. Kuraoka,et al.  Inhibition of nucleotide excision repair by anti-XPA monoclonal antibodies which interfere with binding to RPA, ERCC1, and TFIIH. , 2004, Biochemical and biophysical research communications.

[157]  Andrew Pannifer,et al.  Imidazo[1,2-b]pyridazines: a potent and selective class of cyclin-dependent kinase inhibitors. , 2004, Bioorganic & medicinal chemistry letters.

[158]  N. Gusev Some Properties of Caldesmon and Calponin and the Participation of These Proteins in Regulation of Smooth Muscle Contraction and Cytoskeleton Formation , 2001, Biochemistry (Moscow).

[159]  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.

[160]  A Keith Dunker,et al.  Combining prediction, computation and experiment for the characterization of protein disorder. , 2004, Current opinion in structural biology.

[161]  Roded Sharan,et al.  PathBLAST: a tool for alignment of protein interaction networks , 2004, Nucleic Acids Res..

[162]  P. Picotti,et al.  Probing protein structure by limited proteolysis. , 2004, Acta biochimica Polonica.

[163]  Zhang-Zhi Hu,et al.  The iProClass integrated database for protein functional analysis , 2004, Comput. Biol. Chem..

[164]  Lan V. Zhang,et al.  Evidence for dynamically organized modularity in the yeast protein–protein interaction network , 2004, Nature.

[165]  Arun K. Ramani,et al.  Protein interaction networks from yeast to human. , 2004, Current opinion in structural biology.

[166]  T. Galitski Molecular networks in model systems. , 2004, Annual review of genomics and human genetics.

[167]  A. Rao,et al.  Activation and deactivation of gene expression by Ca2+/calcineurin-NFAT-mediated signaling. , 2004, Molecules and cells.

[168]  B. Ason,et al.  A high-throughput assay for Tn5 Tnp-induced DNA cleavage. , 2004, Nucleic acids research.

[169]  A. Fersht,et al.  Crystal Structure of a Superstable Mutant of Human p53 Core Domain , 2004, Journal of Biological Chemistry.

[170]  Ariel Fernández,et al.  The nonconserved wrapping of conserved protein folds reveals a trend toward increasing connectivity in proteomic networks. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[171]  Marc S. Sherman,et al.  Calmodulin Target Database , 2004, Journal of Structural and Functional Genomics.

[172]  D. Storm,et al.  The role of calmodulin as a signal integrator for synaptic plasticity , 2005, Nature Reviews Neuroscience.

[173]  W. Gerthoffer Signal-transduction pathways that regulate visceral smooth muscle function. III. Coupling of muscarinic receptors to signaling kinases and effector proteins in gastrointestinal smooth muscles. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[174]  C. Harris,et al.  p53: traffic cop at the crossroads of DNA repair and recombination , 2005, Nature Reviews Molecular Cell Biology.

[175]  Christopher J. Oldfield,et al.  Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling , 2005, Journal of molecular recognition : JMR.

[176]  Marc S. Cortese,et al.  Coupled folding and binding with α-helix-forming molecular recognition elements , 2005 .

[177]  A. Fink Natively unfolded proteins. , 2005, Current opinion in structural biology.

[178]  A. Rustighi,et al.  Discovering high mobility group A molecular partners in tumour cells , 2005, Proteomics.

[179]  Matthew W. Hahn,et al.  Comparative genomics of centrality and essentiality in three eukaryotic protein-interaction networks. , 2005, Molecular biology and evolution.

[180]  Christian von Mering,et al.  STRING: known and predicted protein–protein associations, integrated and transferred across organisms , 2004, Nucleic Acids Res..

[181]  Paul N Barlow,et al.  Structure of free MDM2 N-terminal domain reveals conformational adjustments that accompany p53-binding. , 2005, Journal of molecular biology.

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

[183]  Cheryl H Arrowsmith,et al.  Characterization of segments from the central region of BRCA1: an intrinsically disordered scaffold for multiple protein-protein and protein-DNA interactions? , 2005, Journal of molecular biology.

[184]  M. Vidal,et al.  Effect of sampling on topology predictions of protein-protein interaction networks , 2005, Nature Biotechnology.

[185]  Marc S. Cortese,et al.  Comparing and combining predictors of mostly disordered proteins. , 2005, Biochemistry.