Genetically Engineered Proteins as Recognition Receptors

Chapter

Abstract

The design of fluorescent protein biosensors for the detection of analytes has applications in diverse fields, from molecular life sciences to military readiness. The engineering of biosensors has progressed, from using naturally occurring proteins to the redesign of polypeptide sequences using extensive computational and experimental screening to create entirely new binding molecules. Bacterial periplasmic binding proteins have high affinity and specificity for a variety of biochemically important sugars, amino acids, and anions. The mutation of these proteins and the labeling with fluorescent probes has been utilized to create many reagentless biosensors. Further advances combined genetic fusions of these proteins with derivatives of green fluorescent proteins to create FRET-based biosensors which are expressed in living cells and report on metabolic processes in real-time. A number of proteins and polypeptides have also been used as scaffolds and reengineered to bind new ligands. Computational tools, such as ROSETTA and DEZYMER, have successfully predicted specific mutations to reconstruct protein scaffolds producing novel binders. A complementary approach is to select a highly stable scaffold, randomize predetermined sites, and create phage or ribosome display libraries which may be screened for specificity toward a target analyte. While both of these methods have individually led to the production of novel polypeptides with nanomolar binding constants, the combination of screening libraries and utilizing computational tools is likely to provide the greatest progress in the future of biosensor design.

Keywords

Fluorescence Biosensor Periplasmic binding proteins Affinity receptor Green fluorescent protein FRET Rational design Environmentally-sensitive probes Protein engineering Ligand binding Rosetta DEZYMER Protein scaffold 

Abbreviations

ABD-F

7-Fluorobenz-2-oxa-1,3-diazole-4-sulfonamide

Acrylodan

6-Acryloyl-2-dimetholaminonaphthalene

cAMP

Cyclic-adenosine-5′-monophosphate

Cys

Cysteine

Dapoxyl

(2-Bromoacetamidoethyl)sulfonamide

FAD

Flavin adenine dinucleotide

FRET

Fluorescence resonance energy transfer

IANBD

Ester N-(2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole

IAANS

2-(4′- Iodoacetamido)anilino)naphthalene-6-sulfonatic acid

IAEDANS

5-((((2-Iodacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid

Lys

Lysine

MDCC

7-Diethylamino-3-((((2-aleimidyl)ethyl)amino)carbonyl)coumarin

Met

Methionine

NADH

Nicotinamide adenine dinucleotide

SPR

Surface plasmon resonance

Trp

Tryptophan

References

  1. Abedi MR, Caponigro G, Kamb A (1998) Green fluorescent protein as a scaffold for intracellular presentation of peptides. Nucleic Acids Res 26:623–630Google Scholar
  2. Adams SR, Harootunian AT, Buechler YJ, Taylor SS, Tsien RY (1991) Fluorescence ratio imaging of cyclic amp in single cells. Nature 349:694–697Google Scholar
  3. Allert M, Rizk SS, Looger LL, Hellinga HW (2004) Computational design of receptors for an organophosphate surrogate of the nerve agent soman. Proc Natl Acad Sci USA 101:7907–7912Google Scholar
  4. Baird GS, Zacharias DA, Tsien RY (1999) Circular permutation and receptor insertion within green fluorescent proteins. Proc Natl Acad Sci USA 96:11241–11246Google Scholar
  5. Benson DE, Haddy AE, Hellinga HW (2002) Converting a maltose receptor into a nascent binuclear copper oxygenase by computational design. Biochemistry 41:3262–3269Google Scholar
  6. Benson DE, Wisz MS, Liu W, Hellinga HW (1998) Construction of a novel redox protein by rational design: conversion of a disulfide bridge into a mononuclear iron-sulfur center. Biochemistry 37:7070–7076Google Scholar
  7. Berlman IB (1971) Fluorescence specta of aromatic molecules. Academic, New YorkGoogle Scholar
  8. Beste G, Schmidt FS, Stibora T, Skerra A (1999) Small antibody-like proteins with prescribed ligand specificities derived from the lipocalin fold. Proc Natl Acad Sci USA 96:1898–1903Google Scholar
  9. Binz HK, Amstutz P, Kohl A, Stumpp MT, Briand C, Forrer P, Grutter MG, Pluckthun A (2004) High-affinity binders selected from designed ankyrin repeat protein libraries. Nat Biotechnol 22:575–582Google Scholar
  10. Bjorkman AJ, Binnie RA, Zhang H, Cole LB, Hermodson MA, Mowbray SL (1994) Probing protein–protein interactions. The ribose-binding protein in bacterial transport and chemotaxis. J Biol Chem 269:30206–30211Google Scholar
  11. Bjorkman AJ, Mowbray SL (1998) Multiple open forms of ribose-binding protein trace the path of its conformational change. J Mol Biol 279:651–664Google Scholar
  12. Bloemendal H, de Jong W, Jaenicke R, Lubsen NH, Slingsby C, Tardieu A (2004) Ageing and vision: structure, stability and function of lens crystallins. Prog Biophys Mol Biol 86:407–485Google Scholar
  13. Boas FE, Harbury PB (2007) Potential energy functions for protein design. Curr Opin Struct Biol 17:199–204Google Scholar
  14. Borrok MJ, Kiessling LL, Forest KT (2007) Conformational changes of glucose/galactose-binding protein illuminated by open, unliganded, and ultra-high-resolution ligand-bound structures. Protein Sci 16:1032–1041Google Scholar
  15. Brune M, Hunter JL, Corrie JET, Webb MR (1994) Direct, real-time measrement of rapid inorganic phosphate release using a novel fluorescent probe and its application to actomyosin subfragment atpase. Biochemistry 33:8262–8271Google Scholar
  16. Butterfoss GL, Kuhlman B (2006) Computer-based design of novel protein structures. Annu Rev Biophys Biomol Struct 35:49–65Google Scholar
  17. Chino S, Sakaguchi A, Yamoto R, Ferri S, Sode K (2007) Branched-chain amino acid biosensing using fluorescent modified engineered leucin/isoleucine/valine binding protein. Int J Mol Sci 8:513–525Google Scholar
  18. Cuneo MJ, Changela A, Warren JJ, Beese LS, Hellinga HW (2006) The crystal structure of a thermophilic glucose binding protein reveals adaptations that interconvert mono and di-saccharide binding sites. J Mol Biol 362:259–270Google Scholar
  19. Das R, Baker D (2008) Macromolecular modeling with rosetta. Ann Rev Biochem 77:363–382Google Scholar
  20. Dattelbaum JD, Lakowicz JR (2001) Optical determination of glutamine using a genetically engineered protein. Anal Biochem 291:89–95Google Scholar
  21. Dattelbaum JD, Looger LL, Benson DE, Sali KM, Thompson RB, Hellinga HW (2005) Analysis of allosteric signal transduction mechanisms in an engineered fluorescent maltose biosensor. Protein Sci 14:284–291Google Scholar
  22. deLorimier RM, Smith JJ, Dwyer MA, Looger LL, Sali KM, Paavola CD, Rizk SS, Sadigov S, Conrad DW, Loew L et al (2002) Construction of a fluorescent biosensor family. Protein Sci 11:2655–2675Google Scholar
  23. Der BS, Dattelbaum JD (2008) Construction of a reagentless glucose biosensor using molecular exciton luminescence. Anal Biochem 375:132–140Google Scholar
  24. Deuschle K, Okumoto S, Fehr M, Looger LL, Koszhukh L, Frommer WB (2005) Construction and optimization of a family of genetically encoded metabolite sensors by semirational protein engineering. Protein Sci 14:2304–2314Google Scholar
  25. DiPilato LM, Cheng X, Zhang J (2004) Fluorescent indicators of camp and epac activation reveal differential dynamics of camp signaling within discrete subcellular compartments. Proc Natl Acad Sci USA 101:15081–15086Google Scholar
  26. Dogan J, Lendel C, Hard T (2006) Thermodynamics of folding and binding in an affibody: affibody complex. J Mol Biol 359:1305–1315Google Scholar
  27. Doornbos RMP, Lang R, Aalders MC, Cross FW, Sterenborg HJCM (1999) The determination of in vivo human tissue optical properties and absolute chromophore concentrations using spatially resolved steady-state diffuse reflectance spectroscopy. Phys Med Biol 44:967–981Google Scholar
  28. Dulla C, Tani H, Okumoto S, Frommer WB, Reimer RJ, Fluguenard JR (2008) Imaging of glutamate in brain slices using fret sensors. J Neurosci Methods 168:306–319Google Scholar
  29. Dwyer MA, Hellinga HW (2004) Periplasmic binding proteins: a versatile superfamily for protein engineering. Curr Opin Struct Biol 14:495–504Google Scholar
  30. Ebersbach H, Fiedler E, Scheuermann T, Fiedler M, Stubbs MT, Reimann C, Proetzel G, Rudolph R, Fiedler U (2007) Affilin-novel binding molecules based on human γ-b-crystallin, an all β-sheet protein. J Mol Biol 372:172–185Google Scholar
  31. Fehr M, Frommer WB, Lalonde S (2002) Visualization of maltose uptake in living yeast cells by fluorescent nanosensors. Proc Natl Acad Sci USA 99:9846–9851Google Scholar
  32. Fehr M, Okumoto S, Deuschle K, Lager I, Looger LL, Persson J, Kozhukh L, Lalonde S, Frommer WB (2005) Development and use of fluorescent nanosensors for metabolite imaging in living cells. Biochem Soc Trans 33:287–290Google Scholar
  33. Ferrer M, Maiolo J, Kratz P, Jackowski JL, Murphy DJ, Delagrave S, Inglese J (2005) Directed evolution of pdz variants to generate high-affinity detection reagents. Protein Eng Des Sel 18:165–173Google Scholar
  34. Flower DR (1996) The lipocalin protein family: structure and function. Biochem J 318:1–14Google Scholar
  35. Friedman M, Nordberg E, Hoiden-Guthenberg I, Brisimar H, Adams GP, Nilsson FY, Carlss J, Stahl S (2007) Phage display selection of affibody molecules with specific binding to the extracellular domain of the epidermal growth factor receptor. Protein Eng Des Sel 20:189–199Google Scholar
  36. Friedman M, Orlova A, Johansson E, Eriksson TLJ, Hoiden-Guthenberg I, Tolmachev V, Nilsson FY, Stahl S (2008) Directed evolution to low nanomolar affinity of a tumor-targeting epidermal growth factor receptor-binding affibody molecule. J Mol Biol 376:1388–1402Google Scholar
  37. Gasymov OK, Abduragimov AR, Glasgow BJ (2008) Ligand binding site of tear lipocalin: contribution of a trigonal cluster of, charged residues probed by 8-anilino-1-naphthalenesulfonic acid. Biochemistry 47:1414–1424Google Scholar
  38. Ge X, Tolosa L, Rao G (2004) Dual-labeled glucose binding protein for ratiometric measurements of glucose. Anal Chem 76:1403–1410Google Scholar
  39. Ge X, Tolosa L, Simpson J, Rao G (2003) Genetically engineered binding proteins as biosensors for fermentation and cell culture. Biotechnol Bioeng 84:723–731Google Scholar
  40. Gelly JC, Gracy J, Kaas Q, Le-Nguyen D, Heitz A, Chiche L (2004) The knottin website and database: a new information system dedicated to the knottin scaffold. Nucleic Acids Res 32:D156–D159Google Scholar
  41. Giebel LB, Cass RT, Milligan DL, Young DC, Arze R, Johnson CR (1995) Screening of cyclic peptide phage libraries identifies ligands that bind streptavidin with high affinities. Biochemistry 34:15430–15435Google Scholar
  42. Gilardi G, Mei G, Rosato N, Agro AF, Cass AE (1997) Spectroscopic properties of an engineered maltose binding protein. Protein Eng 10:479–486Google Scholar
  43. Gilardi G, Zhou LQ, Hibbert L, Cass AE (1994) Engineering the maltose binding protein for reagentless fluorescence sensing. Anal Chem 66:3840–3847Google Scholar
  44. Goh YT, Frecer V, Ho B, Ding JL (2002a) Rational desing of green fluorescent protein mutants as biosensor for bacterial endotoxin. Protein Eng Des Sel 15:493–502Google Scholar
  45. Goh YT, Ho B, Ding JL (2002b) A novel fluorescent protein-based biosensor for gram-negative bacteria. Appl Environ Microbiol 68:6343–6352Google Scholar
  46. Gronwall C, Jonsson A, Lindstrom S, Gunneriusson E, Stahl S, Herne N (2007) Selection and characterization of affibody ligands binding to alzheimer amyloid beta peptides. J Biotech 128:162–183Google Scholar
  47. Gu H, Lalonde S, Okumoto S, Looger LL, Scharff-Poulsen AM, Grossman AR, Kossmann J, Jakobsen I, Frommer WB (2006) A novel analytical method for in vivo phosphate tracking. FEBS Lett 580:5885–5893Google Scholar
  48. Gunnarsson LC, Karlsson EN, Albrekt AS, Andersson M, Holst O, Ohlin M (2004) A carbohydrated binding module as a diversity-carrying scaffold. Protein Eng Des Sel 17:213–221Google Scholar
  49. Gunnarsson LC, Karlsson EN, Andersson M, Holst O, Ohlin M (2006) Molecular engineering of a thermostable carbohydrate-binding module. Biocatal Biotransformation 24:31–37Google Scholar
  50. Ha JS, Song JJ, Lee YM, Kim SJ, Sohn JH, Shin CS, Lee SG (2007) Design and application of highly responsive fluorescence resonance energy transfer biosensors for detection of sugar in living saccharomyces cerevisiae cells. Appl Environ Microbiol 73:7408–7414Google Scholar
  51. He JJ, Quiocho FA (1993) Dominant role of local dipoles in stabilizing uncompensated charges on a sulfate sequestered in a periplasmic active transport protein. Protein Sci 2:1643–1647Google Scholar
  52. Heitz A, Le-Nguyen D, Chiche L (1999) Min-21 and min-23, the smallest peptides that fold like a cystine-stabilized β-sheet motif: design, solution structure, and thermal stability. Biochemistry 38:10615–10625Google Scholar
  53. Hellinga HW, Richards FM (1991) Construction of new ligand binding sites in proteins of known structure. I. Computer-aided modeling of sites with pre-defined geometry. J Mol Biol 222:763–785Google Scholar
  54. Hendrickson TL, de Crecy-Lagard V, Schimmel P (2004) Incorporation of nonnatural amino acids into proteins. Annu Rev Biochem 73:147–176Google Scholar
  55. Herman RE, Badders D, Fuller M, Makienko EG, Houston ME, Quay SC, Johnson PH (2007) The trp cage motif as a scaffold for the display of a randomized peptide library on bacteriophage t7. J Biol Chem 282:9813–9824Google Scholar
  56. Higgins CF (1992) Abc transporters: from microorganisms to man. Annu Rev Cell Biol 8:67–113Google Scholar
  57. Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR (1989) Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene 77:51–59Google Scholar
  58. Hsiao CD, Sun UJ, Rose J, Wang B-C (1996) The crystal structure of glutamine-binding protein from Escherichia coli. J Mol Biol 262:225–242Google Scholar
  59. Huang J, Koide A, Nettle KW, Greene GL, Koide S (2006) Conformation-specific affinity purification of proteins using engineered binding proteins: application to the estrogen receptor. Protein Expr Purif 47:348–354Google Scholar
  60. Hufton SE, van Neer N, van den Beuken T, Desmet J, Sablon E, Hoogenboom HR (2000) Development and application of cytotoxic t lymphocyte-associated antigen 4 as a protein scaffold for the generation of novel binding ligands. FEBS Lett 475:225–231Google Scholar
  61. Itoh RE, Kurokawa K, Ohba Y, Yoshizaki H, Mochizuki N, Masuda M (2002) Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol Cell Biol 22:6582–6591Google Scholar
  62. Karatan E, Merguerian M, Han Z, Scholle MD, Koide S, Kay BK (2004) Molecular recognition properties of fn3 monobodies that bind the src sh3 domain. Chem Biol 11:835–844Google Scholar
  63. Kasha M (1963) Energy transfer mechanisms and the molecular exciton model for molecular aggregates. Radiat Res 20:55–71Google Scholar
  64. Kawe M, Forrer P, Amstutz P, Pluckthun A (2006) Isolation of intracellular proteinase inhibitors derived from designed ankyrin repeat proteins by genetic screening. J Biol Chem 281:40252–40263Google Scholar
  65. Khan F, Gunudi L, Pickup JC (2008) Fluorescence-based sensing of glucose using engineered glucose/galactose-binding protein: a comparison of fluorescence resonance energy transfer and environmentally sensitive dye labeling strategies. Biochem Biophys Res Commun 365:102–106Google Scholar
  66. Kiczak L, Kasztura M, Koscielska-Kasprzak K, Kadlez M, Otlewsdi J (2001) Selection of potent chymotrypsin and elastase inhibitors from m13 phage library of basic pancreatic trypsin inhibitor (bpti). Biochim Biophys Acta 17:153–163Google Scholar
  67. Klotz IM (1997) Ligand-receptor energetics: a guide for the perplexed. Wiley, New YorkGoogle Scholar
  68. Kohl A, Binz HK, Forrer P, Stumpp MT, Pluckthun A, Grutter MG (2003) Designed to be stable: crystal structure of a consensus ankyrin repeat protein. Proc Natl Acad Sci USA 100:1700–1705Google Scholar
  69. Koide A, Bailey CW, Huang X, Koide S (1998) The fibronectin type iii domain as a scaffold for novel binding proteins. J Mol Biol 284:1141–1151Google Scholar
  70. Korndorfer IP, Schlehuber S, Skerra A (2003) Structural mechanism of specific ligand recognition by a lipocalin tailored for the complexation of digoxigenin. J Mol Biol 330:385–396Google Scholar
  71. Lakowicz JR (1994) Emerging biomedical applications of time-resolved fluorescence spectroscopy. In: Lakowicz JR (ed) Topics in fluorescence spectroscopy, vol 4, Probe design and chemical sensing. Plenum, New York, p 501Google Scholar
  72. Lakowicz JR (1999) Principles of fluorescence spectroscopy. Plenum, New YorkGoogle Scholar
  73. Lalonde S, Ehrhardt DW, Frommer WB (2005) Shining light on signaling and metabolic networks by genetically encoded biosensors. Curr Opin Plant Biol 8:574–581Google Scholar
  74. Lehtio J, Teeri TT, Nygren PA (2002) Alpha-amylase inhibitors selected from a combinatorial library of a cellulose binding domain scaffold. Proteins 41:316–322Google Scholar
  75. Lendel C, Dogan J, Hard T (2006) Structural basis for molecular recognition in an affibody: affibody complex. J Mol Biol 359:1293–1304Google Scholar
  76. Lin KF, Lee PH, Hsu MP, Chen CS, Lyu PC (2007) Structure-based protein engineering for α-amylase inhibitory activity of plant defensin. Proteins 68:530–540Google Scholar
  77. Looger LL, Dwyer MA, Smith JJ, Hellinga HW (2003) Computational design of receptor and sensor proteins with novel functions. Nature 423:185–190Google Scholar
  78. Looger LL, Hellinga HW (2001) Generalized dead-end elimination algorithms make large-scale protein side-chain structure prediction tractable: implications for protein design and structural genomics. J Mol Biol 307:429–445Google Scholar
  79. Looger LL, Lalonde S, Frommer WB (2005) Genetically encoded fret sensors for visualizing metabolites with subcellular resolution in living cells. Plant Physiol 138:555–557Google Scholar
  80. Luo KQ, Yu VC, Pu Y, Chang DC (2001) Application of the fluorescence resonance energy transfer method for studying the dynamics of caspase-3 activation during uv-induced apoptosis in living hela cells. Biochem Biophys Res Commun 283:1054–1060Google Scholar
  81. Malabarba MG, Milia E, Faretta M, Zamponi R, Pelicci PG, Di Fiore PP (2001) A repertoire library that allows the selection of synthetic sh2s with altered binding specificities. Oncogene 20:5186–5194Google Scholar
  82. Mansouri S, Schultz JS (1984) A minature optical glucose sensor based on affinity binding. Biotechnolgy 2:885–890Google Scholar
  83. Markland W, Ley AC, Lee SW, Ladner RC (1996a) Iterative optimization of high-affinity protease inhibitors using phage display.1. Plasmin. Biochemistry 35:8045–8057Google Scholar
  84. Markland W, Ley AC, Ladner RC (1996b) Iterative optimization of high-affinity protease inhibitors using phage display. 2. Plasma kallikrein and thrombin. Biochemistry 35:8058–8067Google Scholar
  85. Marvin JS, Corcoran EE, Hattangadi NA, Zhang JV, Gere SA, Hellinga HW (1997) The rational design of allosteric interactions in a monomeric protein and its applications to the construction of biosensors. Proc Natl Acad Sci USA 94:4366–4371Google Scholar
  86. Marvin JS, Hellinga HW (1998) Engineering biosensors by introducing fluorescent allosteric signal transducers: construction of a novel glucose sensor. J Am Chem Soc 120:7–11Google Scholar
  87. Marx KA (2003) Quartz crystal microbalance: a useful tool for studying thin polymer films and complex biomolecular systems at the solution-surface interface. Biomacromolecules 4:1099–1120Google Scholar
  88. McConnell SJ, Hoess RH (1995) Tendamistat as a scaffold for confomationally constrained phage peptide libraries. J Mol Biol 250:460–470Google Scholar
  89. Meadows D, Schultz JS (1988) Fiber-optic biosensors based on flurescence energy transfer. Talanta 35:145–150Google Scholar
  90. Mitra RD, Silva CM, Youvan DC (1996) Fluorescence resonance energy transfer between blue-emitting and red-shifted excitation derivatives of the green fluorescent protein. Gene 173:13–17Google Scholar
  91. Miyawaki A, Griesbeck O, Heim R, Tsien RY (1999) Dynamic and quantitative ca2+ measurements using improved cameleons. Proc Natl Acad Sci USA 96:2135–2140Google Scholar
  92. Mizuno T, Murao K, Tanabe Y, Oka M, Tanaka T (2007) Metal-ion-dependent gfp emission in vivo by combining a circularly permutated green fluorescent protein with an engineered metal-ion-binding coiled-coil. J Am Chem Soc 129:11378–11383Google Scholar
  93. Moschou EA, Sharma BV, Deo SK, Daunert S (2004) Fluorescence glucose detection: advances towards the ideal in vivo biosensor. J Fluoresc 14:535–547Google Scholar
  94. Nakai J, Ohkura M, Imoto K (2001) A high signal-to-noise ca2+ probe composed of a single green fluorescent protein. Nat Biotechnol 19:137–141Google Scholar
  95. Nalbant P, Hodgson L, Kraynov V, Toutchkine A, Hahn KM (2004) Activation of endogenous cdc42 visualized in living cells. Science 305:1615–1619Google Scholar
  96. Neidigh JW, Fesinmeyer RM, Andersen NH (2002) Designing a 20-residue protein. Nat Struct Biol 9:425–430Google Scholar
  97. Newman JD, Turner AP (2005) Home blood glucose biosensors: a commerical perspective. Biosens Bioelectron 20:2435–2453Google Scholar
  98. Nilsson B, Moks T, Jansson B, Abrahmsen L, Elmblad A, Holmgren E, Henrichson C, Jones TA, Uhlen M (1987) A synthetic igg-binding domain based on staphylococcal protein-a. Protein Eng Des Sel 1:107–113Google Scholar
  99. Nord K, Gunneriusson E, Ringdahl J, Stahl S, Uhlen M, Nygren PA (1997) Binding proteins selected from combinatorial libraries of an alpha-helical bacterial receptor domain. Nat Biotechnol 15:772–777Google Scholar
  100. Nuttall SD, Rousch MJ, Irving SE, Hufton SE, Hoogenboom HR, Hudson PJ (1999) Design and expression of soluble ctla-4 variable domain as a scaffold for the display of functional polypeptides. Proteins 36:217–227Google Scholar
  101. Oh BH, Pandit J, Kang CH, Nikaido K, Gokcen S, Ames GF, Kim SH (1993) Three-dimensional structures of the periplasmic lysine/arginine/ornithine-binding protein with and without a ligand. J Biol Chem 268:11348–11355Google Scholar
  102. Ohkura M, Matsuzaki M, Kasai H, Imoto K, Nakai J (2005) Genectically encoded bright ca2+ probe applicable for dynamic ca2+ imaging of dendritic spines. Anal Chem 77:5861–5869Google Scholar
  103. Orlova A, Feldwisch J, Abrahmsen L, Tolmachev V (2007) Affibody molecules for molecular imaging and therapy for cancer. Cancer Biother Radiopharm 22:573–584Google Scholar
  104. Phillips GN (2006) The three-dimensional structure of green fluorescent protein and its implications for function and design. Methods Biochem Anal 47:67–82Google Scholar
  105. Quiocho FA, Spurlino JC, Rodseth LE (1997) Extensive features of tight oligosaccharide binding revealed in high-resolution structures of the maltodextrin transport/chemosensory receptor. Structure 5:997–1015Google Scholar
  106. Quiocho FA, Vyas NK (1984) Novel stereospecificity of the l-arabinose-binding protein. Nature 310:381–386Google Scholar
  107. Ramoni R, Bellucci S, Grycznyski I, Grycznyski Z, Grolli S, Staiano M, De Bellis G, Micciulla F, Pastore R, Tiberia A et al (2007) The protein scaffold of the lipocalin odorant-binding protein is suitable for the design of new biosensors for the detection of explosive components. J Phys Condens Matter 19:395012 (7pp) doi: 10.1088/0953-8984/19/39/395012Google Scholar
  108. Richards J, Miller M, Abend J, Koide A, Koide S, Dewhurst S (2003) Engineered fibronectin type iii domain with a rgdwxe sequence binds with enhanced affinity and specificity to human vβ3 integrin. J Mol Biol 326:1475–1488Google Scholar
  109. Richmond TA, Takahashi TT, Shimkhada R, Bernsdorf J (2005) Engineered metal binding sites on green fluorescence protein. Biochem Biophys Res Commun 268:462–465Google Scholar
  110. Romoser VA, Hinkle PM, Persechini A (1997) Detection in living cells of ca2+-dependent changes in the fluorescence emission of an indicator composed of two green fluorescent protein variants linked by a calmodulin-binding sequence. J Biol Chem 272:13270–13274Google Scholar
  111. Sakaguchi A, Ferri S, Tsugawa W, Sode K (2007) Novel fluorescent sensing systme for alpha-fructosyl amino acids based on engineered fructosyl amino acid binding protein. Biosens Bioelectron 22:1933–1938Google Scholar
  112. Salins LL, Deo SK, Daunert S (2004) Phosphate binding protein as the biorecognition element in a biosensor for phosphate. Sens Actuators B Chem 97:81–89Google Scholar
  113. Salins LL, Goldsmith ES, Ensor CM, Daunert S (2002) A fluorescence-based sensing system for the environmental monitoring of nickel using the nickel binding protein from Escherichia coli. Anal Bioanal Chem 372:174–180Google Scholar
  114. Salins LL, Ware RA, Ensor CM, Daunert S (2001) A novel reagentless sensing system for measuring glucose based on the galactose/glucose-binding protein. Anal Biochem 294:19–26Google Scholar
  115. Sato M, Ozawa T, Inukai K, Asano T, Umezawa Y (2002) Fluorescent indicators for imaging protein phosphorylation in single living cells. Nat Biotechnol 20:287–294Google Scholar
  116. Schlehuber S, Beste G, Skerra A (2000) A novel type of receptor protein, based on the lipocalin scaffold, with specificity for digoxigenin. J Mol Biol 297:1105–1120Google Scholar
  117. Schneider S, Buchert M, Georgiev O, Catimel B, Halford M, Stacker SA, Baechi T, Moelling K, Hovens CM (1999) Mutagenesis and selection of pdz domains that bind new protein targets. Nat Biotechnol 17:170–175Google Scholar
  118. Schweizer A, Roschitzki-Voser H, Amstutz P, Briand C, Gulotti-Georgieva M, Prenosil E, Binz HK, Capitani G, Baici A, Pluckthun A et al (2007) Inhibition of caspase-2 by a designed ankyrin repeat protein: specificity, structure, and inhibition mechanism. Structure 15:625–636Google Scholar
  119. Sedgwick SG, Smerdon SJ (1999) The ankyrin repeat: a diversity of interactions on a common structural framework. Trends Biochem Sci 24:311–316Google Scholar
  120. Selsted ME, Ouellette AJ (2005) Mammalian defensins in the antimicrobial immune response. Nat Immunol 6:551–557Google Scholar
  121. Sharff AJ, Rodseth LE, Spurlino JC, Quiocho FA (1992) Crystallographic evidence of a large ligand-induced hinge-twist motion between the two domains of the maltodextrin binding protein involved in active transport and chemotaxis. Biochemistry 31:10657–10663Google Scholar
  122. Shrestha S, Salins LL, Ensor CM, Daunert S (2002) Rationally designed fluorescently labeled sulfate-binding protein mutants: evaluation in the development of a sensing system for sulfate. Biotechnol Bioeng 78:517–526Google Scholar
  123. Silverman J, Lu Q, Bakker A, To W, Duguay A, Alba BM, Smith R, Rivas A, Li P, Le H et al (2005) Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains. Nat Biotechnol 23:1556–1561Google Scholar
  124. Smith GP, Patel SU, Windass JD, Thornton JM, Winter G, Griffiths AD (1998) Small binding proteins selected from a combinatorial repertoire of knottins displayed on phage. J Mol Biol 277:317–332Google Scholar
  125. Sohanpal K, Watsuji T, Zhou LQ, Cass AEG (1993) Reagentless fluorescence sensors based upon specific binding proteins. Sens Actuators B Chem 11:547–552Google Scholar
  126. Souriau C, Chiche L, Irving R, Hudson P (2005) New binding specificities derived from min-23, a small cystine-stabilized peptidic scaffold. Biochemistry 44:7143–7155Google Scholar
  127. Souslova EA, Belousov VV, Lock JG, Stromblad S, Kasparov S, Bolshakov A, Pinelis VG, Labas YA, Lukyanov S, Mayr LM et al (2007) Single fluorescent protien-based ca2+ sensors with increased dynamic range. BMC Biotechnol 7:37Google Scholar
  128. Staiano M, Scognamiglio V, Mamone G, Rossi M, Parracino A, Rossi M, D’Auria S (2006) Glutamine-binding protein from escherichia coli specifically binds a wheat gliadin peptides. 2. Resonance energy transfer studies suggest a new sensing approach for an easy detection of wheat gliadin. J Proteome Res 5:2083–2086Google Scholar
  129. Stec B (2006) Plant thionins – the structural perspective. Cell Mol Life Sci 63:1370–1385Google Scholar
  130. Stumpp MT, Forrer P, Binz HK, Pluckthun A (2003) Designing repeat proteins: modular leucine-rich repeat protein libraries based on the mammalian ribonuclease inhibitor family. J Mol Biol 332:471–487Google Scholar
  131. Sumner JP, Westerber NM, Stoddard AK, Hurst TK, Cramer M, Thompson RB, Fierke CA, Kopelman R (2006) Dsred as a highly sensitive, selective, and reversible fluorescence-based biosensor for both cu+ and cu2+ ions. Biosens Bioelectron 21:1302–1308Google Scholar
  132. Sun Y-J, Rose J, Wang B-C, Hsiao C-D (1998) The structure of glutamine-binding protein complexed with glutamine at 1.94 a resolution: compaisons with other amino acid binding proteins. J Mol Biol 278:219–229Google Scholar
  133. Thomas KJ, Sherman DB, Amiss TJ, Andalus SA, Pitner B (2006) A long-wavelength fluorescent glucose biosensor based on bioconjugates of galactose/glucose binding protein and nile red derivatives. Diabetes Technol Ther 8:261–268Google Scholar
  134. Tolosa L, Gryczynski I, Eichhorn LR, Dattelbaum JD, Castellano FN, Rao G, Lakowicz JR (1999) Glucose sensor for low-cost lifetime-based sensing using a genetically engineered protein. Anal Biochem 267:114–120Google Scholar
  135. Trakhanov S, Vyas NK, Luecke H, Kristensen DM, Ma J, Quiocho FA (2005) Ligand-free and -bound structures of the binding protein (livj) of the escherichia coli abc leucine/isoleucine/valine transport system: trajectory and dynamics of the interdomain rotation and ligand specificity. Biochemistry 44:6597–6608Google Scholar
  136. Tran T, Engfeldt T, Orlova A, Sandstrom M, Feldwisch J, Abrahmsen L, Wennborg A, Tolmachev V, Karlstrom AE (2007) Tc-99 m-maeee-z(her2: 342), an affibody molecule-based tracer for the detection of her2 expression in malignant tumors. Bioconjug Chem 18:1956–1964Google Scholar
  137. Tsien RY (1998) The green fluorescent protein. Annu Rev Biochem 67:509–544Google Scholar
  138. Vercillo NC, Herald KJ, Fox JF, Der BS, Dattelbaum JD (2007) Analysis of ligand binding to a ribose biosensor using site-directed mutagenesis and fluorescence spectroscopy. Protein Sci 16:362–368Google Scholar
  139. Vermersch PS, Lemon DD, Tesmer JJ, Quiocho FA (1991) Sugar-binding and crystallographic studies of an arabinose-binding protein mutant (met108leu) that exhibits enhanced affinity and altered specificity. Biochemistry 30:6861–6866Google Scholar
  140. Vita C, Drakopoulou I, Vizzavona J, Rochette S, Martin L, Menez A, Roumestand C, Yang YS, Ylisastigui L, Benjouad A et al (1999) Rational engineering of a miniprotein that reproduces the core of the cd4 site interacting with hiv-1 envelope glycoprotein. Proc Natl Acad Sci USA 96:13091–13096Google Scholar
  141. Vita C, Roumestand C, Toma F, Menez A (1995) Scorpion toxins as natureal scaffolds for protein engineering. Proc Natl Acad Sci USA 92:6404–6408Google Scholar
  142. Voigt CA, Gordon B, Mayo SL (2000) Trading accuracy for speed: a quantitative comparison of search algorithms in protein sequence design. J Mol Biol 299:789–803Google Scholar
  143. Vopel S, Muhlbach H, Skerra A (2005) Rational engineering of a fluorescein-binding anticalin for improved ligand affinity. Biol Chem 386:1097–1104Google Scholar
  144. Wang Y, Botvinick EL, Zhao Y, Berns MW, Usami S, Tsien RY, Chien S (2005) Visualizing the mechanical activation of src. Nature 434:1040–1045Google Scholar
  145. Wang Y, Shyy JY, Chien S (2008) Fluorescence proteins, live-cell imaging, and mechanobiology: seeing is believing. Ann Rev Biomed Eng 10:1–38MATHGoogle Scholar
  146. Wang Z, Luecke H, Yao N, Quiocho FA (1997) A low energy short hydrogen bond in very high resolution structures of protein receptor–phosphate complexes. Nat Struct Biol 4:519–522Google Scholar
  147. Ward WW (2006) Biochemical and physical properties of green fluorescent protein. Methods Biochem Anal 47:39–65Google Scholar
  148. Weber G (1952a) Polarization of the fluorescence of macromolecules 1. Theory and experimental methods. Biochem J 51:145–155Google Scholar
  149. Weber G (1952b) Polarization of the fluorescence of macromolecules 2. Fluorescent conjugates of ovalbumin and bovine serum albumin. Biochem J 51:155–167Google Scholar
  150. West JB (ed) (1990) Best and taylor’s physiological basis of medical practice. Williams & Wilkins, Baltimore, MDGoogle Scholar
  151. White SH, Wimley WC, Selsted ME (1995) Structure, function, and membrane integration of defensins. Curr Opin Struct Biol 5:521–527Google Scholar
  152. Yang W, Wilkins AL, Ye Y, Liu Z, Li S, Urbauer JL, Hellinga HW, Kearnery A, van der Merwe PA, Yang JJ (2005) Design of a calcium-binding protein with desired structure in a cell adhesion molecules. J Am Chem Soc 127:2085–2093Google Scholar
  153. Yao N, Ledvina PS, Choudhary A, Quiocho FA (1996) Modulation of a salt link does not affect binding of phosphate to its specific active transport receptor. Biochemistry 35:2079–2085Google Scholar
  154. Yao N, Trakhanov S, Quiocho FA (1994) Refined 1.89-a structure of the histidine-binding protein complexed with histidine and its relationship with many other active transport/chemosensory proteins. Biochemistry 33:4769–4779Google Scholar
  155. Ye K, Schultz JS (2003) Genetic engineering of an allosterically based glucose indicator protein for continuous glucose monitoring by fluorescence resonance energy transfer. Anal Chem 75:3119–3127Google Scholar
  156. Zahnd C, Pecorari F, Straumann N, Wyler E, Pluckthun A (2006) Selection and characterization of her2 binding-designed ankyrin repeat proteins. J Biol Chem 281:35167–35175Google Scholar
  157. Zahnd C, Wyler E, Schwenk JM, Steiner D, Lawrence MC, McKern NM, Pecorari F, Ward CW, Joos TO, Pluckthun A (2007) A designed ankyrin repeat protein evolved to picomolar affinity to her2. J Mol Biol 369:1015–1028Google Scholar
  158. Zhang J, Ma Y, Taylor SS, Tsien RY (2001) Genetically encoded reporters of protein kinase a activity reveal impact of substrate tethering. Proc Natl Acad Sci USA 98:14997–145002Google Scholar
  159. Zhao A, Xue Y, Zhang J, Gao B, Feng J, Mao C, Zheng L, Liu M, Wang F, Wang H (2004) A conformation-constrained peptide library based on insect defensin a. Peptides 25:629–635Google Scholar
  160. Zhou LQ, Cass AE (1991) Periplasmic binding protein based biosesnors. 1. Preliminary study of maltose binding protein as sensing element for maltose biosensor. Biosens Bioelectron 6:445–450Google Scholar
  161. Zukin RS, Hartig PR, Koshland DE (1979) Effect of an induced conformational change on the physical properties of two chemotactic receptor molecules. Biochemistry 18:5599–5605Google Scholar
  162. Zukin RS, Hartig PR, Koshland DE Jr (1977) Use of a distant reporter group as evidence for a conformational change in a sensory receptor. Proc Natl Acad Sci USA 74:1932–1936Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of RichmondRichmondUSA

Personalised recommendations