1469-896X/asset/olbannerleft.gif?v=1&s=d218899ae53b2862ab119790ed504b8d72122fb3)
1469-896X/asset/olbannerright.gif?v=1&s=59470eb9a1d9b7b13b1be75e9445e6c46ee2214f)
Review
You have full text access to this OnlineOpen article
Knitting and untying the protein network: Modulation of protein ensembles as a therapeutic strategy
Article first published online: 29 DEC 2008
DOI: 10.1002/pro.43
Copyright © 2008 The Protein Society
Additional Information
How to Cite
Gordo, S. and Giralt, E. (2009), Knitting and untying the protein network: Modulation of protein ensembles as a therapeutic strategy. Protein Science, 18: 481–493. doi: 10.1002/pro.43
Publication History
- Issue published online: 23 FEB 2009
- Article first published online: 29 DEC 2008
- Accepted manuscript online: 29 DEC 2008 12:00AM EST
- Manuscript Accepted: 24 NOV 2008
- Manuscript Revised: 16 OCT 2008
- Manuscript Received: 11 JUL 2008
Funded by
- Plan Nacional del Ministerio de Educación y Ciencia. Grant Number: BIO2008-0799
- Generalitat de Catalunya—Xarxa de Referencia en Biotechnologia
References
- 1, , , ( 2005) Interactome: gateway into systems biology. Hum Mol Genet 14: R171–R181.
- 2, , , ( 2001) Lethality and centrality in protein networks. Nature 411: 41–42.
- 3, ( 2006) Why do hubs tend to be essential in protein networks? PLoS Genet 2: e88.
- 4, ( 1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J Mol Biol 293: 321–331.
- 5( 2002) Natively unfolded proteins: a point where biology waits for physics. Protein Sci 11: 739–756.Direct Link:
- 6, ( 2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6: 197–208.
- 7, , , , ( 2005) Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J 272: 5129–5148.Direct Link:
- 8, ( 2006) Disordered domains and high surface charge confer hubs with the ability to interact with multiple proteins in interaction networks. FEBS Lett 580: 2041–2045.
- 9, , , ( 2003) From words to literature in structural proteomics. Nature 422: 216–225.
- 10, ( 2000) Structural symmetry and protein function. Annu Rev Biophys Biomol Struct 29: 105–153.
- 11( 1991) Inside a living cell. Trends Biochem Sci 16: 203–206.
- 12, , , ( 2008) Principles of protein–protein interactions: what are the preferred ways for proteins to interact? Chem Rev 108: 1225–1244.
- 13, ( 2003a) Diversity of protein–protein interactions. EMBO J 22: 3486–3492.
- 14, ( 2003b) Structural characterisation and functional significance of transient protein–protein interactions. J Mol Biol 325: 991–1018.
- 15, ( 2003) Analysing six types of protein–protein interfaces. J Mol Biol 325: 377–387.
- 16, , ( 1999) The atomic structure of protein–protein recognition sites. J Mol Biol 285: 2177–2198.
- 17, , , ( 2005) Interaction preferences across protein–protein interfaces of obligatory and non-obligatory components are different. BMC Struct Biol 5: 15.
- 18, , , ( 2001) Residue frequencies and pairing preferences at protein-protein interfaces. Proteins 43: 89–102.Direct Link:
- 19, , ( 2005) Hot regions in protein–protein interactions: the organization and contribution of structurally conserved hot spot residues. J Mol Biol 345: 1281–1294.
- 20, ( 1994) Cavities and packing at protein interfaces. Protein Sci 3: 2194–2206.Direct Link:
- 21( 2006) Water structure and interactions with protein surfaces. Curr Opin Struct Biol 16: 152–159.
- 22, , , , ( 2007) The molecular architecture of protein–protein binding sites. Curr Opin Struct Biol 17: 67–76.
- 23, ( 2007) Characterization of interfacial solvent in protein complexes and contribution of wet spots to the interface description. Proteins 67: 1087–1095.Direct Link:
- 24( 1997) Protein–protein interactions: interface structure, binding thermodynamics, and mutational analysis. Chem Rev 97: 1233–1250.
- 25, , , ( 2008) Similar chemistry, but different bond preferences in inter versus intra-protein interactions. Proteins 72: 741–753.Direct Link:
- 26, , , ( 2000) Conservation of polar residues as hot spots at protein interfaces. Proteins 39: 331–342.Direct Link:
- 27, , ( 1997) Hydrogen bonds and salt bridges across protein–protein interfaces. Protein Eng 10: 999–1012.
- 28( 2003) Hydrophobic tendencies of polar groups as a major force in molecular recognition. Biopolymers 70: 492–496.Direct Link:
- 29, , , , ( 2006) Specificity of molecular interactions in transient protein–protein interaction interfaces. Proteins 65: 593–606.Direct Link:
- 30, , , ( 2004) A dissection of specific and non-specific protein-protein interfaces. J Mol Biol 336: 943–955.
- 31, ( 2007) How different are structurally flexible and rigid binding sites? Sequence and structural features discriminating proteins that do and do not undergo conformational change upon ligand binding. J Mol Biol 365: 257–273.
- 32( 2002) Kinetic studies of protein–protein interactions. Curr Opin Struct Biol 12: 41–47
- 33, ( 1985) Diffusion-controlled macromolecular interactions. Annu Rev Biophys Chem 14: 131–160.
- 34, ( 1996) Rapid, electrostatic assisted association of proteins. Nat Struct Biol 3: 427–431.
- 35, , , , , ( 1998) Electrostatic enhancement of diffusion-controlled protein–protein association: comparison of theory and experiment on barnase and barstar. J Mol Biol 278: 1015–1024.
- 36, , ( 2000) Electrostatic aspects of protein–protein interactions. Curr Opin Struct Biol 10: 153–159.
- 37, ( 2008) Electrostatic rate enhancement and transient complex of protein-protein association. Proteins 71: 320–335.Direct Link:
- 38( 2003) Disease proteomics. Nature 422: 226–232.
- 39, , ( 2007) Human protein–protein interaction networks and the value for drug discovery. Drug Discov Today 12: 709–716.
- 40, , , ( 2007) Protein–protein interactions and disease: use of S. cerevisiae as a model system. Biochim Biophys Acta 1774: 838–847.
- 41, , , , , ( 2007) The human disease network. Proc Natl Acad Sci USA 104: 8685–8690.
- 42, , ( 2005) Protein misfolding, aggregation, and degradation in disease. Mol Biotechnol 31: 141–150.
- 43( 2006) Protein misfolding disorders: pathogenesis and intervention. J Inherit Metab Dis 29: 456–470.
- 44, ( 2003) Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J Mol Med 81: 678–699.
- 45, ( 2003) Quality control and protein folding in the secretory pathway. Annu Rev Cell Dev Biol 19: 649–676.
- 46, , ( 1996) Proteasome-dependent endoplasmic reticulum-associated protein degradation: an unconventional route to a familiar fate. Proc Natl Acad Sci USA 93: 13797–13801.
- 47, , , , , ( 2000) Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404: 770–774.
- 48, , , ( 2004) Pharmacologic rescue of conformationally-defective proteins: implications for the treatment of human disease. Traffic 5: 821–837.Direct Link:
- 49, ( 2006) Protein-misfolding diseases and chaperone-based therapeutic approaches. FEBS J 273: 1331–1349.Direct Link:
- 50( 1999) Protein misfolding, evolution and disease. Trends Biochem Sci 24: 329–332.
- 51, , ( 2003) From Alzheimer to Huntington: why is a structural understanding so difficult? EMBO J 22: 355–361.
- 52, ( 2003) Therapeutic approaches to protein–misfolding diseases. Nature 426: 905–909.
- 53( 1998) What holds us together? Why do some of us fall apart? What can we do about it? Matrix Biol 16: 519–528.
- 54
- 55, , ( 2004) Systems biology in drug discovery. Nat Biotechnol 22: 1253–1259.
- 56
- 57( 2007) Structural biology, protein conformations and drug designing. Curr Protein Pept Sci 8: 376–380.
- 58( 2002) The chemical biology of apoptosis. Exploring protein–protein interactions and the life and death of cells with small molecules. Chem Biol 9: 1059–1072.
- 59, ( 2004) Small-molecule inhibitors of protein–protein interactions: progressing towards the dream. Nat Rev Drug Discov 3: 301–317.
- 60( 2006) Drugs targeting protein–protein interactions. Chem Med Chem 1: 400–411.
- 61, ( 2007) Reaching for high-hanging fruit in drug discovery at protein–protein interfaces. Nature 450: 1001–1009.
- 62, ( 2007) Protein–protein interaction inhibitors: small molecules from screening techniques. Curr Top Med Chem 7: 922–927.
- 63, , , , , ( 2002) Protein–protein interactions: mechanisms and modification by drugs. J Mol Recognit 15: 405–422.Direct Link:
- 64, , , ( 2007) Strategies to search and design stabilizers of protein–protein interactions: a feasibility study. Proteins 68: 170–186.Direct Link:
- 65, ( 2007) Chemical control over protein-protein interactions: beyond inhibitors. Comb Chem High Throughput Screen 10: 667–675.
- 66, , ( 1998) Human antibodies by design. Nat Biotechnol 16: 535–539.
- 67, ( 1997) Scaffolds for engineering novel binding sites in proteins. Curr Opin Struct Biol 7: 463–469.
- 68, ( 2005) Molecular recognition with designed peptides and proteins. Curr Opin Chem Biol 9: 627–631.
- 69, ( 1997) Nucleic acid selection and the challenge of combinatorial chemistry. Chem Rev 97: 349–370.
- 70, , ( 1998) From peptides to drugs via phage display. Drug Discov Today 3: 370–378.
- 71, , ( 2003) Exploring protein–protein interactions with phage display. Chembiochem 4: 14–25.Direct Link:
- 72, ( 2006) Targeting protein–protein interactions with small molecules: challenges and perspectives for computational binding epitope detection and ligand finding. Curr Med Chem 13: 2607–2625.
- 73, , ( 2007) Computational identification of inhibitors of protein–protein interactions. Curr Top Med Chem 7: 63–82.
- 74, ( 2005) Design and structure of peptide and peptidomimetic antagonists of protein–protein interaction. Curr Protein Pept Sci 6: 151–169.
- 75, , ( 2007) Scaffolds for blocking protein–protein interactions. Curr Top Med Chem 7: 928–942.
- 76, ( 2005) Protein surface recognition and proteomimetics: mimics of protein surface structure and function. Curr Opin Chem Biol 9: 632–638.
- 77, , ( 2007) Synthetic non-peptide mimetics of alpha-helices. Chem Soc Rev 36: 326–334.
- 78, , ( 2007) Modulation of protein–protein interactions by stabilizing/mimicking protein secondary structure elements. Curr Top Med Chem 7: 33–62.
- 79
- 80, , , , , ( 2000) High-affinity pentavalent ligands of Escherichia coli heat-labile enterotoxin by modular structure-based design. J Am Chem Soc 122: 2663–2664.
- 81, , , , ( 2003) Protein surface recognition by rational design: nanomolar ligands for potassium channels. J Am Chem Soc 125: 12668–12669.
- 82, , , , , , , , , , , , , , ( 1998) Novel and specific respiratory syncytial virus inhibitors that target virus fusion. J Med Chem 41: 2671–2675.
- 83, , , , ( 2001) Surface recognition of a protein using designed transition metal complexes. J Am Chem Soc 123: 6283–6290.
- 84, ( 2000) Design of growth factor antagonists with antiangiogenic and antitumor properties. Oncogene 19: 6566–6573.
- 85, , ( 1999) Ru(bpy)3-based artificial receptors toward a protein surface: selective binding and efficient photoreduction of cytochrome c. Chem Comm 2345–2346.
- 86, , , , ( 2002) Influencing receptor-ligand binding mechanisms with multivalent ligand architecture. J Am Chem Soc 124: 14922–14933.
- 87, , ( 1998) Synthetic activation of caspases: artificial death switches. Proc Natl Acad Sci USA 95: 3655–3660.
- 88, , , , , ( 1996) Inhibiting transthyretin amyloid fibril formation via protein stabilization. Proc Natl Acad Sci USA 93: 15051–15056.
- 89, , , , , , ( 2008) J Stability and structural recovery of the tetramerization domain of p53-R337H mutant induced by a designed templating ligand. Proc Natl Acad Sci USA 105: 16426–16431.
- 90
- 91, , ( 2006) Peptide-based inhibitors of amyloid assembly. Methods Enzymol 413: 273–312.
- 92( 2002) Chemical chaperones: a pharmacological strategy for disorders of protein folding and trafficking. Pediatr Res 52: 832–836.
- 93, , , ( 2006) Small molecule pharmacological chaperones: from thermodynamic stabilization to pharmaceutical drugs. Biochim Biophys Acta 1764: 1677–1687.
- 94
- 95
- 96( 2006) Therapy through chaperones: sense or antisense? Cystic fibrosis as a model disease. J Inherit Metab Dis 29: 477–487.
- 97( 1997) p53, the cellular gatekeeper for growth and division. Cell 88: 323–331.
- 98, ( 2005) p53: traffic cop at the crossroads of DNA repair and recombination. Nat Rev Mol Cell Biol 6: 44–55.
- 99, , , , , , , , ( 2007) Quaternary structures of tumor suppressor p53 and a specific p53 DNA complex. Proc Natl Acad Sci USA 104: 12324–12329.
- 100
- 101, , ( 2006) The P53 pathway: what questions remain to be explored? Cell Death Differ 13: 1027–1036.
- 102, , , , , , , ( 1994) p53 domains: structure, oligomerization, and transformation. Mol Cell Biol 14: 5182–5191.
- 103( 1995) Flexibility: the key to p53 function? Trends Biochem Sci 20: 49–51.
- 104, , , , ( 2002) p53 contains large unstructured regions in its native state. J Mol Biol 322: 917–927.
- 105, ( 2007) Structure-function-rescue: the diverse nature of common p53 cancer mutants. Oncogene 26: 2226–2242.
- 106, , ( 2006) Some p53-binding proteins that can function as arbiters of life and death. Cell Death Differ 13: 984–993.
- 107, ( 2001) Rescuing the function of mutant p53. Nat Rev Cancer 1: 68–76.
- 108, , , , , , ( 2007) Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 28: 622–629.Direct Link:
- 109
- 110, , , ( 2001) Functional cross-talk of HIV-1 Tat with p53 through its C-terminal domain. Biochem Biophys Res Commun 287: 556–561.
- 111, , , ( 1995) Reciprocal modulations between p53 and Tat of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 92: 5461–5464.
- 112, , ( 2000) Strategies for manipulating the p53 pathway in the treatment of human cancer. Biochem J 352: 1–17.
- 113, ( 2007) Reactivation of mutant p53: molecular mechanisms and therapeutic potential. Oncogene 26: 2243–2254.
- 114( 2003) Inhibiting the p53-MDM2 interaction: an important target for cancer therapy. Nat Rev Cancer 3: 102–109.
- 115, , , , , , , , , , , ( 2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303: 844–848.
- 116, ( 2007) Targeting protein–protein interactions: lessons from p53/MDM2. Biopolymers 88: 657–686.Direct Link:
- 117, ( 2007) Small molecule protein–protein inhibitors for the p53-MDM2 interaction. Curr Top Med Chem 7: 952–960.
- 118, , , ( 1999) Pharmacological rescue of mutant p53 conformation and function. Science 286: 2507–2510.
- 119, , , , , , ( 2001) Amifostine (WR2721) restores transcriptional activity of specific p53 mutant proteins in a yeast functional assay. Oncogene 20: 3533–3540.
- 120, ( 2003) Novel cancer therapy by reactivation of the p53 apoptosis pathway. Ann Med 35: 458–465.
- 121( 2006) Adenovirus p53 gene therapy. Expert Opin Biol Ther 6: 55–61.