DARPins and other repeat protein scaffolds: Advances in engineering and applications

Current Opinion in Biotechnology

Volumn 22, Issue 6, 2011, Pages 849-857

  Boersma, Ykelien L ^a   Plückthun, Andreas ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTIVE IMMUNE SYSTEMS; BINDING PROTEINS; MODERN TECHNOLOGIES; NOVEL APPLICATIONS; PROTEIN ENGINEERING; PROTEIN-PROTEIN INTERACTIONS; SPECIFIC BINDING;

ANTIBODIES; GENETIC ENGINEERING;

SCAFFOLDS (BIOLOGY);

ADENOVIRUS VECTOR; ANKYRIN; ARMADILLO DOMAIN PROTEIN; CETUXIMAB; DESIGNED ANKYRIN REPEAT PROTEIN; EPITHELIAL CELL ADHESION MOLECULE; HEAT REPEAT PROTEIN; LENTIVIRUS VECTOR; RECOMBINANT PROTEIN; SCAFFOLD PROTEIN; TETRATRICOPEPTIDE REPEAT PROTEIN; UNCLASSIFIED DRUG;

ALPHA HELIX; AMINO TERMINAL SEQUENCE; ANTINEOPLASTIC ACTIVITY; BINDING AFFINITY; CARBOXY TERMINAL SEQUENCE; CRYSTAL STRUCTURE; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG TARGETING; GENETIC TRANSFECTION; IMMUNOHISTOCHEMISTRY; NONHUMAN; PEPTIDE ANALYSIS; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN ENGINEERING; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN STABILITY; PROTEIN TARGETING; REVIEW; SENSITIVITY AND SPECIFICITY; STRUCTURE ANALYSIS; TUMOR DIAGNOSIS; VIRAL GENE DELIVERY SYSTEM;

ANIMALS; HUMANS; NEOPLASMS; PEPTIDE LIBRARY; PROTEIN ENGINEERING; PROTEIN TRANSPORT; PROTEINS; REPETITIVE SEQUENCES, AMINO ACID;

VERTEBRATA;

EID: 80054856259     PISSN: 09581669     EISSN: 18790429     Source Type: Journal    
DOI: 10.1016/j.copbio.2011.06.004     Document Type: Review

References (80)

1. Löfblom J., Stahl S. Non-immunoglobulin based protein scaffolds. Curr Opin Biotechnol 2011, 10.1016/j.copbio.2011.06.002.
2. Gill D.S., Damle N.K. Biopharmaceutical drug discovery using novel protein scaffolds. Curr Opin Biotechnol 2006, 17:653-658.
3. Nygren P., Skerra A. Binding proteins from alternative scaffolds. J Immunol Methods 2004, 290:3-28.
4. Binz H.K., Amstutz P., Plückthun A. Engineering novel binding proteins from nonimmunoglobulin domains. Nat Biotechnol 2005, 23:1257-1268.
5. Kobe B., Kajava A.V. The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 2001, 11:725-732.
6. D'Andrea L., Regan L. TPR proteins: the versatile helix. Trends Biochem Sci 2003, 28:655-662.
7. Andrade M., Petosa C., O'Donoghue S., Müller C., Bork P. Comparison of ARM and HEAT protein repeats. J Mol Biol 2001, 209:1-18.
8. Li J., Mahajan A., Tsai M. Ankyrin repeat: a unique motif mediating protein-protein interactions. Biochemistry 2006, 45:15168-15178.
9. Al-Khodor S., Price C.T., Kalia A., Abu Kwaik Y. Functional diversity of ankyrin repeats in microbial proteins. Trends Microbiol 2010, 18:132-139.
10. Bella J., Hindle K.L., McEwan P.A., Lovell S.C. The leucine-rich repeat structure. Cell Mol Life Sci 2008, 65:2307-2333.
11. Pancer Z., Cooper M.D. The evolution of adaptive immunity. Annu Rev Immunol 2006, 24:497-518.
12. Grove T.Z., Cortajarena A.L., Regan L. Ligand binding by repeat proteins: natural and designed. Curr Opin Struct Biol 2008, 18:507-515.
13. Main E.R.G., Lowe A.R., Mochrie S.G.J., Jackson S.E., Regan L. A recurring theme in protein engineering: the design, stability and folding of repeat proteins. Curr Opin Struct Biol 2005, 15:464-471.
14. Stumpp M.T., Forrer P., Binz H.K., Plückthun A. Designing repeat proteins: modular leucine-rich repeat protein libraries based on the mammalian ribonuclease inhibitor family. J Mol Biol 2003, 332:471-487.
15. Binz H., Stumpp M.T., Forrer P., Amstutz P., Plückthun A. Designing repeat proteins: well-expressed, soluble and stable proteins from combinatorial libraries of consensus ankyrin repeat proteins. J Mol Biol 2003, 332:489-503.
16. Main E.R.G., Jackson S.E., Regan L. The folding and design of repeat proteins: reaching a consensus. Curr Opin Struct Biol 2003, 13:482-489.
17. Urvoas A., Guellouz A., Valerio-Lepiniec M., Graille M., Durand D., Desravines D.C., van Tilbeurgh H., Desmadril M., Minard P. Design, production and molecular structure of a new family of artificial alpha-helicoidal repeat proteins (αRep) based on thermostable HEAT-like repeats. J Mol Biol 2010, 404:307-327.
18. Parmeggiani F., Pellarin R., Larsen A.P., Varadamsetty G., Stumpp M.T., Zerbe O., Caflisch A., Plückthun A. Designed armadillo repeat proteins as general peptide-binding scaffolds: consensus design and computational optimization of the hydrophobic core. J Mol Biol 2008, 376:1282-1304.
19. Forrer P., Stumpp M.T., Binz H.K., Plückthun A. A novel strategy to design binding molecules harnessing the modular nature of repeat proteins. FEBS Lett 2003, 539:2-6.
20. Mosavi L.K., Minor D.L., Peng Z.Y. Consensus-derived structural determinants of the ankyrin repeat motif. Proc Natl Acad Sci U S A 2002, 99:16029-16034.
21. Kohl A., Binz H., Forrer P., Stumpp M.T., Plückthun A., Grütter M.G. Designed to be stable: crystal structure of a consensus ankyrin repeat protein. Proc Natl Acad Sci U S A 2003, 100:1700-1705.
22. Interlandi G., Wetzel S.K., Settanni G., Plückthun A., Caflisch A. Characterization and further stabilization of designed ankyrin repeat proteins by combining molecular dynamics simulations and experiments. J Mol Biol 2008, 375:837-854.
23. Wetzel S.K., Settanni G., Kenig M., Binz H., Plückthun A. Folding and unfolding mechanism of highly stable full consensus ankyrin repeat proteins. J Mol Biol 2008, 376:241-257.
24. Merz T., Wetzel S.K., Firbank S., Plückthun A., Grütter M.G., Mittl P.R. Stabilizing ionic interactions in a full consensus ankyrin repeat protein. J Mol Biol 2008, 376:232-240.
25. Kramer M.A., Wetzel S.K., Plückthun A., Mittl P.R., Grütter M.G. Structural determinants for improved stability of designed ankyrin repeat proteins with a redesigned C-capping module. J Mol Biol 2010, 404:381-391.
26. Wetzel S.K., Ewald C., Settanni G., Jurt S., Plückthun A., Zerbe O. Residue-resolved stability of full-consensus ankyrin repeat proteins probed by NMR. J Mol Biol 2010, 402:241-258.
27. Julien O., Gignac I., Hutton A., Yee A., Arrowsmith C.H., Gagné S.M. MTH187 from Methanobacterium thermoautotrophicum has three HEAT-like repeats. J Biomol NMR 2006, 35:149-154.
28. Andrade M.A., Perez-Iratxeta C., Ponting C.P. Protein repeats: structures, functions, and evolution. J Struct Biol 2001, 134:117-131.
29. Kippert F., Gerloff D.L. Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH. PLoS ONE 2009, 4:e7148.
30. Cortajarena A.L., Regan L. Ligand binding by TPR domains. Protein Sci 2006, 15:1193-1198.
31. Main E.R.G., Xiong Y., Cocco M.J., D'Andrea L., Regan L. Design of stable alpha-helical arrays from an idealized TPR motif. Structure 2003, 11:497-508.
32. Main E.R.G., Stott K., Jackson S.E., Regan L. Local and long-range stability in tandemly arrayed tetratricopeptide repeats. Proc Natl Acad Sci U S A 2005, 102:5721-5726.
33. Tripp K.W., Barrick D. Enhancing the stability and folding rate of a repeat protein through the addition of consensus repeats. J Mol Biol 2007, 365:1187-1200.
34. Kajander T., Cortajarena A.L., Main E.R.G., Mochrie S.G.J., Regan L. A new folding paradigm for repeat proteins. J Am Chem Soc 2005, 127:10188-10190.
35. Cortajarena A.L., Mochrie S.G., Regan L. Mapping the energy landscape of repeat proteins using NMR-detected hydrogen exchange. J Mol Biol 2008, 379:617-626.
36. Cortajarena A.L., Regan L. Calorimetric study of a series of designed repeat proteins: modular structure and modular folding. Protein Sci 2011, 20:336-340.
37. Jackrel M.E., Cortajarena A.L., Liu T.Y., Regan L. Screening libraries to identify proteins with desired binding activities using a split-GFP reassembly assay. ACS Chem Biol 2010, 5:553-562.
38. Grove T.Z., Hands M., Regan L. Creating novel proteins by combining design and selection. Protein Eng Des Sel 2010, 23:449-455.
39. Magliery T.J., Wilson C.G.M., Pan W., Mishler D., Ghosh I., Hamilton A.D., Regan L. Detecting protein-protein interactions with a green fluorescent protein fragment reassembly trap: scope and mechanism. J Am Chem Soc 2005, 127:146-157.
40. Nibbering P.H., Zomerdijk T.P., Corsèl-Van Tilburg A.J., Van Furth R. Mean cell volume of human blood leucocytes and resident and activated murine macrophages. J Immunol Methods 1990, 129:143-145.
41. Dreier B., Plückthun A. Ribosome display: a technology for selecting and evolving proteins from large libraries. Methods Mol Biol 2011, 687:283-306.
42. Plückthun A: Ribosome display: a perspective. Methods Mol Biol 2001, in press.
43. Zahnd C., Sarkar C.A., Plückthun A. Computational analysis of off-rate selection experiments to optimize affinity maturation by directed evolution. Protein Eng Des Sel 2010, 23:175-184.
44. Hanes J., Jermutus L., Plückthun A. Selecting and evolving functional proteins in vitro by ribosome display. Methods Enzymol 2000, 328:404-430.
45. Zahnd C., Amstutz P., Plückthun A. Ribosome display: selecting and evolving proteins in vitro that specifically bind to a target. Nat Methods 2007, 4:269-279.
46. Amstutz P., Binz H.K., Parizek P., Stumpp M.T., Kohl A., Grütter M.G., Forrer P., Plückthun A. Intracellular kinase inhibitors selected from combinatorial libraries of designed ankyrin repeat proteins. J Biol Chem 2005, 280:24715-24722.
47. Amstutz P., Koch H., Binz H., Deuber S.A., Plückthun A. Rapid selection of specific MAP kinase-binders from designed ankyrin repeat protein libraries. Protein Eng Des Sel 2006, 19:219-229.
48. Bandeiras T.M., Hillig R.C., Matias P.M., Eberspaecher U., Fanghänel J., Thomaz M., Miranda S., Crusius K., Pütter V., Amstutz P., et al. Structure of wild-type Plk-1 kinase domain in complex with a selective DARPin. Acta Crystallogr D Biol Crystallogr 2008, 64:339-353.
49. Milovnik P., Ferrari D., Sarkar C.A., Plückthun A. Selection and characterization of DARPins specific for the neurotensin receptor 1. Protein Eng Des Sel 2009, 22:357-366.
50. Sennhauser G., Amstutz P., Briand C., Storchenegger O., Grütter M.G. Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors. PLoS Biol 2007, 5:e7.
51. Zahnd C., Wyler E., Schwenk J.M., Steiner D., Lawrence M.C., McKern N.M., Pecorari F., Ward C.W., Joos T.O., Pluckthun A. A designed ankyrin repeat protein evolved to picomolar affinity to Her2. J Mol Biol 2007, 369:1015-1028.
52. Eggel A., Baumann M.J., Amstutz P., Stadler B.M., Vogel M. DARPins as bispecific receptor antagonists analyzed for immunoglobulin E receptor blockage. J Mol Biol 2009, 393:598-607.
53. Eggel A., Buschor P., Baumann M.J., Amstutz P., Stadler B.M., Vogel M. Inhibition of ongoing allergic reactions using a novel anti-IgE DARPin-Fc fusion protein. Allergy 2011, 66:961-968.
54. Baumann M.J., Eggel A., Amstutz P., Stadler B.M., Vogel M. DARPins against a functional IgE epitope. Immunol Lett 2010, 133:78-84.
55. Schweizer A., Rusert P., Berlinger L., Ruprecht C.R., Mann A., Corthésy S., Turville S.G., Aravantinou M., Fischer M., Robbiani M., et al. CD4-specific designed ankyrin repeat proteins are novel potent HIV entry inhibitors with unique characteristics. PLoS Pathog 2008, 4:e1000109.
56. Dreier B., Mikheeva G., Belousova N., Parizek P., Boczek E., Jelesarov I., Forrer P., Plückthun A., Krasnykh V. Her2-specific multivalent adapters confer designed tropism to adenovirus for gene targeting. J Mol Biol 2011, 405:410-426.
57. Steiner D., Forrer P., Stumpp M., Plückthun A. Signal sequences directing cotranslational translocation expand the range of proteins amenable to phage display. Nat Biotechnol 2006, 24:823-831.
58. Steiner D., Forrer P., Plückthun A. Efficient selection of DARPins with sub-nanomolar affinities using SRP phage display. J Mol Biol 2008, 382:1211-1227.
59. Nangola S., Minard P., Tayapiwatana C. Appraisal of translocation pathways for displaying ankyrin repeat protein on phage particles. Protein Expr Purif 2010, 74:156-161.
60. Paschke M., Höhne W. A twin-arginine translocation (Tat)-mediated phage display system. Gene 2005, 350:79-88.
61. Dröge M.J., Boersma Y.L., Braun P., Buining R.J., Julsing M.K., Selles K.G.A., van Dijl J.M., Quax W.J. Phage display of an intracellular carboxylesterase of Bacillus subtilis: a comparison of the Sec and Tat pathway capabilities. Appl Environ Microbiol 2006, 72:4589-4594.
62. Speck J., Arndt K.M., Müller K.M. Efficient phage display of intracellularly folded proteins mediated by the TAT pathway. Protein Eng Des Sel 2011, 24:473-484.
63. Huber T., Steiner D., Rothlisberger D., Plückthun A. In vitro selection and characterization of DARPins and Fab fragments for the co-crystallization of membrane proteins: the Na+-citrate symporter CitS as an example. J Struct Biol 2007, 159:206-221.
64. Sennhauser G., Grütter M.G. Chaperone-assisted crystallography with DARPins. Structure 2008, 16:1443-1453.
65. Warke A., Momany C. Addressing the protein crystallization bottleneck by cocrystallization. Cryst Growth Des 2007, 7:2219-2225.
66. Münch R.C., Mühlebach M.D., Schaser T., Kneissl S., Jost C., Plückthun A., Cichutek K., Buchholz C.J. DARPins: an efficient targeting domain for lentiviral vectors. Mol Ther 2011, 19:686-693.
67. Theurillat J., Dreier B., Nagy-Davidescu G., Seifert B., Behnke S., Zürrer-Härdi U., Ingold F., Plückthun A., Moch H. Designed ankyrin repeat proteins: a novel tool for testing epidermal growth factor receptor 2 expression in breast cancer. Mod Pathol 2010, 23:1289-1297.
68. Winkler J., Martin-Killias P., Plückthun A., Zangemeister-Wittke U. EpCAM-targeted delivery of nanocomplexed siRNA to tumor cells with designed ankyrin repeat proteins. Mol Cancer Ther 2009, 8:2674-2683.
69. Martin-Killias P., Stefan N., Rothschild S., Plückthun A., Zangemeister-Wittke U. A novel fusion toxin derived from an EpCAM-specific designed ankyrin repeat protein has potent anti-tumor activity. Clin Cancer Res 2011, 17:100-110.
70. Zahnd C., Kawe M., Stumpp M.T., de Pasquale C., Tamaskovic R., Nagy-Davidescu G., Dreier B., Schibli R., Binz H.K., Waibel R., et al. Efficient tumor targeting with high-affinity designed ankyrin repeat proteins: effects of affinity and molecular size. Cancer Res 2010, 70:1595-1605.
71. Schmidt M.M., Wittrup K.D. A modeling analysis of the effects of molecular size and binding affinity on tumor targeting. Mol Cancer Ther 2009, 8:2861-2871.
72. Adams G.P., Schier R., McCall A.M., Simmons H.H., Horak E.M., Alpaugh R.K., Marks J.D., Weiner L.M. High affinity restricts the localization and tumor penetration of single-chain Fv antibody molecules. Cancer Res 2001, 61:4750-4755.
73. Rudnick S.I., Lou J., Shaller C.C., Tang Y., Klein-Szanto A.J.P., Weiner L.M., Marks J.D., Adams G.P. Influence of affinity and antigen internalization on the uptake and penetration of anti-HER2 antibodies in solid tumors. Cancer Res 2011, 71:2250-2259.
74. Cortajarena A.L., Wang J., Regan L. Crystal structure of a designed tetratricopeptide repeat module in complex with its peptide ligand. FEBS J 2010, 277:1058-1066.
75. Cortajarena A.L., Yi F., Regan L. Designed TPR modules as novel anticancer agents. ACS Chem Biol 2008, 3:161-166.
76. Andrade M.A., Bork P. HEAT repeats in the Huntington's disease protein. Nat Genet 1995, 11:115-116.
77. Wieschaus E., Riggleman R. Autonomous requirements for the segment polarity gene armadillo during Drosophila embryogenesis. Cell 1987, 49:177-184.
78. Sikorski R.S., Boguski M.S., Goebl M., Hieter P. A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 1990, 60:307-317.
79. Breeden L., Nasmyth K. Similarity between cell-cycle genes of budding yeast and fission yeast and the Notch gene of Drosophila. Nature 1987, 329:651-654.
80. Michaely P., Bennett V. The membrane-binding domain of ankyrin contains four independently folded subdomains, each comprised of six ankyrin repeats. J Biol Chem 1993, 268:22703-22709.