Advertisement

Protein–Protein Interactions

  • Hae Ryoun Park
  • Lisa Montoya Cockrell
  • Yuhong Du
  • Andrea Kasinski
  • Jonathan Havel
  • Jing Zhao
  • Francisca Reyes-Turcu
  • Keith D. Wilkinson
  • Haian Fu
Protocol
Part of the Springer Protocols Handbooks book series (SPH)

1. Introduction

Diverse cellular processes are mediated by dynamic networks of interacting proteins in living organisms (1,2). These highly regulated protein–protein interactions determine cellular functions that are fundamental to life. As increasing numbers of protein complexes and interconnected protein networks are revealed by a variety of experimental approaches, general principles underlying protein–protein interactions and their roles in controlling cellular processes have emerged. It appears that a general mode of protein–protein interaction is mediated by a diverse group of specialized protein modules within individual proteins (2). These protein modules often contain sequence motifs and structures conserved throughout evolution. The efficient regulation of many protein interactions is achieved in part by posttranslational modification of a specific protein motif, such as phosphorylation of a protein motif generating a new binding site for other proteins. For example, Src...

Keywords

Protein Interaction Surface Plasmon Resonance Fluorescence Polarization Yellow Fluorescent Protein Bait Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Papin JA, et al (2005) Reconstruction of cellular signalling networks and analysis of their properties. Nat Rev Mol Cell Biol 6(2):99–111PubMedCrossRefGoogle Scholar
  2. 2.
    Pawson T Nash P (2003) Assembly of cell regulatory systems through protein interaction domains. Science 300(5618):445–452PubMedCrossRefGoogle Scholar
  3. 3.
    Fu H, Subramanian RR, Masters SC (14-3-3) proteins: structure, function, and regulation. Annu Rev Pharmacol Toxicol 40:617–647Google Scholar
  4. 4.
    Raman M Cobb MH (2003) MAP kinase modules: many roads home. Curr Biol,13(22) R886–888PubMedCrossRefGoogle Scholar
  5. 5.
    Arkin MR Wells JA, (2004) Small-molecule inhibitors of protein–protein interactions: progressing towards the dream. Nat Rev Drug Discov 3(4):301–317PubMedCrossRefGoogle Scholar
  6. 6.
    Fu H, (2004) Protein–protein interactions: methods and applications Totowa, NJ: Humana PressGoogle Scholar
  7. 7.
    Golemis E, Adams PD (2005) Protein–protein interactions: a molecular cloning manual Cold Spring Harbor, NY: Cold Spring Harbor PublisherGoogle Scholar
  8. 8.
    Sarbassov DD, et al (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB Mol Cell 22(2):159–168Google Scholar
  9. 9.
    Harlow E, Lane D (eds.) (1996) Antibodies – a laboratory manual. Cold Spring Harbor LaboratoryGoogle Scholar
  10. 10.
    Spector DL, Goldman RD, Leinwand LA (1997) Cells, a laboratory manual Cold Spring Harbor Laboratory PressGoogle Scholar
  11. 11.
    Ausubel FM, et al (1987) Current protocols in molecular biology New York, NY: WileyGoogle Scholar
  12. 12.
    Dudek H et al (1997) Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 275(5300):661–665PubMedCrossRefGoogle Scholar
  13. 13.
    Masters SC, Fu H (2001) 14-3-3 proteins mediate an essential anti-apoptotic signal. J Biol Chem 276(48):45193–45200PubMedCrossRefGoogle Scholar
  14. 14.
    Guan KL, Dixon JE (1991) Eukaryotic proteins expressed in Escherichia coli: an improved thrombin cleavage and purification procedure of fusion proteins with glutathione S-transferase. Anal Biochem 192(2):262–267PubMedCrossRefGoogle Scholar
  15. 15.
    Rigaut G, Chevchenko A, Rutz B, Wilm M, Mann M, Seraphin B (1999) A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol 17(10):1030–1032PubMedCrossRefGoogle Scholar
  16. 16.
    Puig O, Caspary F, Rigaut G, Rutz B, Bouveret E, Bragado-Nilsson E, Wilm M, Seraphin B (2001) The tandem affinity purification(TAP) method: a general procedure of protein complex purification. Methods 24(3):218–229PubMedCrossRefGoogle Scholar
  17. 17.
    Gould KL, Ren L, Feoktistova AS, Jennings JL, Link AJ (2004) Tandem affinity purification and identification of protein complex components. Methods 33(3): 239–244PubMedCrossRefGoogle Scholar
  18. 18.
    Liu X, Constantinescu SN, Sun Y, Bogan JS, Hirsch D, Weinberg RA, Lodish HF (2000) Generation of mammalian cells stably expressing multiple genes at predetermined levels. Anal Biochem 280(1):20–28PubMedCrossRefGoogle Scholar
  19. 19.
    Benzinger A, Muster N, Koch HB, Yates JR, Hermeking H (2005) Targeted pro-teomic analysis of 14-3-3 sigma, a p53 effector commonly silenced in cancer. Mol Cell Proteomics 4(6):785–795PubMedCrossRefGoogle Scholar
  20. 20.
    Burckstummer T, Bennett K, Preradovic A, Schutze G, Hantschel O, Superti-Furga G, Bauch A (2006) An efficient tandem affinity purification procedure for interaction proteomics in mammalian cells. Nat Methods 3(12):1013–1019PubMedCrossRefGoogle Scholar
  21. 21.
    Knuesel M, Wan Y, Xiao Z, Holinger E, Lowe N, Wang W, Liu X (2003) Identification of novel protein–protein interactions using a versatile mammalian tandem affinity purification expression system. Mol Cell Proteomics 2(11):1225–1233PubMedCrossRefGoogle Scholar
  22. 22.
    Koch KV, Reinders Y, Ho T-H, Sickmann A, Graf R (2006) Identification and isolation of Dictyostelium microtubule- associated protein interactions by tandem affinity purification. Eur J Cell Biol 85(9–10):1079–1090PubMedCrossRefGoogle Scholar
  23. 23.
    Hartmann-Petersen R, Gordon C (2005) Quantifying protein–protein interactions in the ubiquitin pathway by surface plasmon resonance. Methods Enzymol 399:164–177PubMedCrossRefGoogle Scholar
  24. 24.
    Katsamba PS, Park S, Laird-Offringa IA (2002) Kinetic studies of RNA-protein interactions using surface plasmon resonance. Methods 26(2):95–104PubMedCrossRefGoogle Scholar
  25. 25.
    Raasi S et al (2004) Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains of HHR23A. J Mol Biol 341(5):1367–1379PubMedCrossRefGoogle Scholar
  26. 26.
    Rich RL, Myszka DG (2000) Advances in surface plasmon resonance biosensor analysis. Curr Opin Biotechnol 11(1):54–61PubMedCrossRefGoogle Scholar
  27. 27.
    Herman B, Krishnan RV, Centonze VE (2004) Microscopic analysis of fluorescence resonance energy transfer (FRET). Methods Mol Biol 261:351–370PubMedGoogle Scholar
  28. 28.
    Clapp AR, Medintz IL, Mattoussi H (2006) Forster resonance energy transfer investigations using quantum-dot fluorophores. Chemphyschem 7(1):47–57PubMedCrossRefGoogle Scholar
  29. 29.
    Selvin PR (2000) The renaissance of fluorescence resonance energy transfer. Nat Struct Biol 7(9):730–734PubMedCrossRefGoogle Scholar
  30. 30.
    Prinz A, Diskar M, Herberg FW (2006) Application of bioluminescence resonance energy transfer (BRET) for biomolecular interaction studies. Chembiochem 7(7):1007–1012PubMedCrossRefGoogle Scholar
  31. 31.
    Ullman EF et al (1994) Luminescent oxygen channeling immunoassay: measurement of particle binding kinetics by chemiluminescence. Proc Natl Acad Sci U S A 91(12):5426–5430PubMedCrossRefGoogle Scholar
  32. 32.
    Wilson J et al (2003) A homogeneous 384-well high- throughput binding assay for a TNF receptor using alphascreen technology. J Biomol Screen 8(5):522–532PubMedCrossRefGoogle Scholar
  33. 33.
    Jameson DM and Croney JC (2003) Fluorescence polarization: past, present and future. Comb Chem High Throughput Screen 6(3):167–173PubMedGoogle Scholar
  34. 34.
    Schade SZ et al (1996) BODIPY-alpha-casein, a pH-independent protein substrate for protease assays using fluorescence polarization. Anal Biochem 243(1):1–7PubMedCrossRefGoogle Scholar
  35. 35.
    Du Y et al (2006) Monitoring 14-3-3 protein interactions with a homogeneous fluorescence polarization assay. J Biomol Screen 11(3):269–276PubMedCrossRefGoogle Scholar
  36. 36.
    Fields S, Song O (1989) A novel genetic system to detect protein–protein interactions. Nature 340(6230):245–6PubMedCrossRefGoogle Scholar
  37. 37.
    Bartel PL, Fields S (1997) The Yeast Two-Hybrid System. Oxford University Press.Google Scholar
  38. 38.
    Gyuris J et al (1993) Cdil, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell 75(4):791–803PubMedCrossRefGoogle Scholar
  39. 39.
    Zhang L et al (1997) Raf-1 kinase and exoenzyme S interact with 14-3-3zeta through a common site involving lysine 49. J Biol Chem 272(21):13717–13724PubMedCrossRefGoogle Scholar
  40. 40.
    Johnsson N, Varshavsky A (1994) Split ubiquitin as a sensor of protein interactions in vivo. Proc Natl Acad Sci U S A 91(22):10340–10344PubMedCrossRefGoogle Scholar
  41. 41.
    Rossi F, Charlton CA, Blau HM (1997) Monitoring protein–protein interactions in intact eukaryotic cells by beta- galactosidase complementation. Proc Natl Acad Sci U S A 94(16):8405–8410PubMedCrossRefGoogle Scholar
  42. 42.
    Remy I, Michnick SW (1999) Clonal selection and in vivo quantitation of protein interactions with protein-fragment complementation assays. Proc Natl Acad Sci U S A 96(10):5394–5399PubMedCrossRefGoogle Scholar
  43. 43.
    Galarneau A et al (2002) Beta-lactamase protein fragment complementation assays as in vivo and in vitro sensors of protein protein interactions. Nat Biotechnol20(6):619–622PubMedCrossRefGoogle Scholar
  44. 44.
    Hu CD, Chinenoy Y, Kerppola TK (2002) Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Mol Cell 9(4):789–798PubMedCrossRefGoogle Scholar
  45. 45.
    Paulmurugan R, Gambhir SS (2005) Novel fusion protein approach for efficient high-throughput screening of small molecule-mediating protein–protein interactions in cells and living animals. Cancer Res 65(16):7413–7420PubMedCrossRefGoogle Scholar
  46. 46.
    Ozawa I et al (2001) Split luciferase as an optical probe for detecting protein– protein interactions in mammalian cells based on protein splicing. Anal Chem 73(11):2516–2521PubMedCrossRefGoogle Scholar
  47. 47.
    Paulmurugan R, Umezawa Y, Gambhir SS (2002) Noninvasive imaging of protein– protein interactions in living subjects by using reporter protein complementation and reconstitution strategies. Proc Natl Acad Sci U S A 99(24):15608–15613PubMedCrossRefGoogle Scholar
  48. 48.
    Luker KE et al (2004) Kinetics of regulated protein– protein interactions revealed with firefly luciferase complementation imaging in cells and living animals. Proc Natl Acad Sci U S A 101(33):12288–12293PubMedCrossRefGoogle Scholar
  49. 49.
    Remy I, Michnick SW (2006) A highly sensitive protein–protein interaction assay based on Gaussia luciferase. Nat Methods 3(12):977–979PubMedCrossRefGoogle Scholar
  50. 50.
    Wehr MC et al (2006) Monitoring regulated protein- protein interactions using split TEV. Nat Methods 3(12):985–993PubMedCrossRefGoogle Scholar
  51. 51.
    Paulmurugan R, Gambhir SS (2003) Monitoring protein- protein interactions using split synthetic renilla luciferase protein-fragment-assisted complementation. Anal Chem, 75(7):1584–1589PubMedCrossRefGoogle Scholar
  52. 52.
    Shumway SD, Li Y, Xiong Y (2003) 14-3-3beta Binds to and Negatively Regulates the Tuberous Sclerosis Complex 2 (TSC2) Tumor Suppressor Gene Product, Tuberin. J Biol Chem 278(4):2089–2092PubMedCrossRefGoogle Scholar
  53. 53.
    Phizicky EM, Fields S (1995) Protein–protein Interactions: Methods for Detection and Analysis. Microbiol Rev 59(1):94–123PubMedGoogle Scholar
  54. 54.
    Zhang L, Chen J, Fu H (1999) Suppression of Apoptosis Signal-Regulating Kinase 1-Induced Cell Death by 14-3-3 Proteins. Proc Natl Acad Sci. USA 96:8511–8515PubMedCrossRefGoogle Scholar
  55. 55.
    Masters S et al (2002) Survival-Promoting Functions of 14-3-3 Proteins. Biochem Soc Trans 30:360–365PubMedCrossRefGoogle Scholar
  56. 56.
    Masters SC et al (1999) Interaction of 14-3-3 with a nonphosphorylated protein lig-and exoenzyme S of Pseudomonas aeruginosa. Biochemistry 38(16):5216–5221.PubMedCrossRefGoogle Scholar
  57. 57.
    Wang H et al (1998) Mutations in the hydrophobic surface of an amphipathic groove of 14-3-3zeta disrupt its interaction with Raf-1 kinase. J Biol Chem 273(26):16297–16304PubMedCrossRefGoogle Scholar
  58. 58.
    Bonnet MC et al (2006) The N-terminus of PKR is Responsible for the Activation of the NF-kappaB Signaling Pathway by Interacting With the IKK Complex. Cell Signal 18(11):1865–1875PubMedCrossRefGoogle Scholar
  59. 59.
    Meek SE, Lane WS, Piwnica-Worms H (2004) Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins. J Biol Chem 279(31):32046–32054PubMedCrossRefGoogle Scholar
  60. 60.
    Blagoev B et al (2003) A proteomics strategy to elucidate functional protein–protein interactions applied to EGF signaling. Nat Biotechnol 21(3):315–318PubMedCrossRefGoogle Scholar
  61. 61.
    Kung LA, Snyder M (2006) Proteome chips for whole- organism assays. Nat Rev Mol Cell Biol 7(8):617–622PubMedCrossRefGoogle Scholar
  62. 62.
    Zhu H et al (2001) Global analysis of protein activities using proteome chips. Science 293(5537):2101–2105PubMedCrossRefGoogle Scholar
  63. 63.
    Jung J W et al (2006) High-throughput analysis of GST- fusion protein expression and activity-dependent protein interactions on GST-fusion protein arrays with a spectral surface plasmon resonance biosensor. Proteomics 6(4):1110–1120PubMedCrossRefGoogle Scholar
  64. 64.
    Keefe AD, Wilson DS, Seelig B, Szostak JW (2001) One-step purification of recombinant proteins using a nanomolar-affinity streptavidin-binding peptide, the SBP-tag. Protein Expression and Purification 23(3):440–446PubMedCrossRefGoogle Scholar
  65. 65.
    Gavin AC, Bosche M, Krause R, Grandi P, Marzioch M, Bauer A, Schultz J, Rick JM, Michon AM, Cruciat CM, Remor M, Hofert C, Schelder M, Brajenovic M, Ruffner H, Merino A, Klein K, Hudak M, Dickson D, Rudi T, Gnau V, Bauch A, Bastuck S, Huhse B, Leutwein C, Heurtier MA, Copley RR, Edelmann A, Querfurth E, Rybin V, Drewes G, Raida M, Bouwmeester T, Bork P, Seraphin B, Kuster B, Neubauer G, and Superti-Furga G (2002) Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415(6868):141–147PubMedCrossRefGoogle Scholar
  66. 66.
    Honey S, Schneider B, Schieltz DM, Yates JR, and Futcher B (2001) A novel multiple affinity purification tag and its use in identification of proteins associated with a cyclin-CDK complex. Nucleic Acids Res 29(4). E24PubMedCrossRefGoogle Scholar
  67. 67.
    Forler D, Kocher T, Rode M, Gentzel M, Izaurralde E, Wilm M (2003) An efficient protein complex purification method for functional proteomics in higher eukaryo-tes. Nat Biotechnol 21(1):89–92PubMedCrossRefGoogle Scholar
  68. 68.
    Drakas R, Prisco M, Baserga R (2005) A modified tandem affinity purification tag technique for the purification of protein complexes in mammalian cells. Proteomics 5(1):132–137PubMedCrossRefGoogle Scholar
  69. 69.
    Schimanski B, Nguyen TN, Gunzl A (2005) Highly efficient tandem affinity purification of trypanosome protein complexes based on a novel epitope combination. Eukaryotic Cell, 4(11):1942–1950PubMedCrossRefGoogle Scholar
  70. 70.
    Krogan NJ, Cagney G, Yu H, Zhong G, Guo X, Ignatchenko A, Li J, Pu S, Datta N, Tikuisis AP, Punna T, Peregrin-Alvarez JM, Shales M, Zhang X, Davey M, Robinson MD, Paccanaro A, Bray JE, Sheung A, Beattie B, Richards DP, Canadien V, Lalev A, Mena F, Wong P, Starostine A, Canete MM, Vlasblom J, Wu S, Orsi C, Collins SR, Chandran S, Haw R, Rilstone JJ, Gandi K, Thompson NJ, Musso G, St Onge P, Ghanny S, Lam MH, Butland G, Altaf-Ul AM, Kanaya S, Shilatifard A, O'Shea E, Weissman JS, Ingles CJ, Hughes TR, Parkinson J, Gerstein M, Wodak SJ, Emili A, and Greenblatt JF (2006) Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature 440(7084):637–643PubMedCrossRefGoogle Scholar
  71. 71.
    Rohila JS, CM, Cerny R, Fromm ME, (2004) Improved tandem affinity purification tag and methods for isolation of protein heterocomplexes from plants. Plant Journal 38(1):172–181PubMedCrossRefGoogle Scholar
  72. 72.
    Raasi S et al (2005) Diverse polyubiquitin interaction properties of ubiquitin-asso-ciated domains. Nat Struct Mol Biol 12(8):708–714PubMedCrossRefGoogle Scholar
  73. 73.
    Hashimoto A, Hirose K, Iino M (2005) BAD detects coincidence of G2/M phase and growth factor deprivation to regulate apoptosis. J Biol Chem 280(28):26225–26232PubMedCrossRefGoogle Scholar
  74. 74.
    Mathis G (1999) HTRF(R) Technology. J Biomol Screen 4(6):309–314PubMedCrossRefGoogle Scholar
  75. 75.
    Liu J et al (2003) A homogeneous in vitro functional assay for estrogen receptors: coactivator recruitment. Mol Endocrinol 17(3):346–355PubMedCrossRefGoogle Scholar
  76. 76.
    Parker GJ et al (2000) Development of high throughput screening assays using fluorescence polarization: nuclear receptor-ligand-binding and kinase/phosphatase assays. J Biomol Screen 5(2):77–88PubMedCrossRefGoogle Scholar
  77. 77.
    Finley RL, Jr, Brent R (1994) Interaction mating reveals binary and ternary connections between Drosophila cell cycle regulators. Proc Natl Acad Sci U S A 91(26):12980–12984PubMedCrossRefGoogle Scholar
  78. 78.
    Parrish JR, Gulyas KD, Finley RL, Jr (2006) Yeast two-hybrid contributions to interactome mapping. Curr Opin Biotechnol 17(4):387–393PubMedCrossRefGoogle Scholar
  79. 79.
    Paulmurugan, R., et al (2004) Molecular imaging of drug-modulated protein–protein interactions in living subjects. Cancer Res 64(6):2113–2119PubMedCrossRefGoogle Scholar
  80. 80.
    Luker KE, Piwnica-Worms D (2004) Optimizing luciferase protein fragment complementation for bioluminescent imaging of protein–protein interactions in live cells and animals. Methods Enzymol 385:349–360PubMedCrossRefGoogle Scholar
  81. 81.
    Mossner E, Koch H, Pluckthun A (2001) Fast selection of antibodies without antigen purification: adaptation of the protein fragment complementation assay to select antigen-antibody pairs. J Mol Biol 308(2):115–122PubMedCrossRefGoogle Scholar
  82. 82.
    Koch H et al (2006) Direct selection of antibodies from complex libraries with the protein fragment complementation assay. J Mol Biol 357(2):427–441PubMedCrossRefGoogle Scholar
  83. 83.
    Remy I, Wilson IA, Michnick SW (1999) Erythropoietin receptor activation by a ligand-induced conformation change. Science, 283(5404):990–993PubMedCrossRefGoogle Scholar
  84. 84.
    Korkhov VM et al (2004) Oligomerization of the {gamma}-aminobutyric acid transporter-1 is driven by an interplay of polar and hydrophobic interactions in transmembrane helix II. J Biol Chem 279(53):p. 55728–36CrossRefGoogle Scholar
  85. 85.
    Lee HK, Dunzendorfer S, Tobias PS (2004) Cytoplasmic domain-mediated dimeri-zations of toll-like receptor 4 observed by beta-lactamase enzyme fragment complementation. J Biol Chem 279(11):10564–10574PubMedCrossRefGoogle Scholar
  86. 86.
    Nyfeler B, Michnick SW, Hauri HP (2005) Capturing protein interactions in the secretory pathway of living cells. Proc Natl Acad Sci U S A 102(18):p. 6350–5CrossRefGoogle Scholar
  87. 87.
    Michnick SW (2003) Protein fragment complementation strategies for biochemical network mapping. Curr Opin Biotechnol 14(6):610–617PubMedCrossRefGoogle Scholar
  88. 88.
    Yu H et al (2003) Measuring drug action in the cellular context using protein-fragment complementation assays. Assay Drug Dev Technol 1(6):811–822PubMedCrossRefGoogle Scholar
  89. 89.
    Michnick SW, Macdonald ML, Westwick JK (2006) Chemical genetic strategies to delineate MAP kinase signaling pathways using protein-fragment complementation assays (PCA). Methods 40(3):287–293PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Hae Ryoun Park
    • 1
  • Lisa Montoya Cockrell
    • 2
  • Yuhong Du
    • 3
  • Andrea Kasinski
    • 2
  • Jonathan Havel
    • 2
  • Jing Zhao
    • 3
  • Francisca Reyes-Turcu
    • 3
  • Keith D. Wilkinson
    • 3
  • Haian Fu
    • 3
  1. 1.Pusan UniversityNamgu, BusanKorea
  2. 2.Graduate Program of Molecular and Systems PharmacologyEmory University School of MedicineAtlantaGA
  3. 3.Department of PharmacologyEmory University School of MedicineAtlantaGA

Personalised recommendations