21
48. Whitaker WR, Davis SA, Arkin AP, Dueber
JE (2012) Engineering robust control
of two- component system phosphotransfer
using modular scaffolds. Proc Natl Acad
Sci 109:18090–18095. doi:10.1073/pnas.
1209230109
49. Skerker JM, Perchuk BS, Siryaporn A et al
(2008) Rewiring the specificity of twocomponent signal transduction systems. Cell
133:1043–1054.
doi:10.1016/j.
cell.2008.04.040
50. Gasser C, Taiber S, Yeh C-M et al (2014)
Engineering of a red-light-activated human
cAMP/cGMP-specific
phosphodiesterase.
Proc Natl Acad Sci 111:8803–8808.
doi:10.1073/pnas.1321600111
51. Lai A, Sato PM, Peisajovich SG (2015)
Evolution of synthetic signaling scaffolds by
recombination of modular protein domains.
ACS Synth Biol 4:714–722. doi:10.1021/
sb5003482
52. Peisajovich SG, Garbarino JE, Wei P, Lim WA
(2010) Rapid diversification of cell signaling
phenotypes by modular domain recombination. Science 328:368–372. doi:10.1126/
science.1182376
53. Wend S, Wagner HJ, Müller K et al (2014)
Optogenetic control of protein kinase activity
in mammalian cells. ACS Synth Biol 3:280–
285. doi:10.1021/sb400090s
54. Wu YI, Frey D, Lungu OI et al (2009) A
genetically encoded photoactivatable Rac
controls the motility of living cells. Nature
461:104–108. doi:10.1038/nature08241
55. Levskaya A, Weiner OD, Lim WA, Voigt CA
(2009) sup: spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 461:997–1001. doi:10.1038/
nature08446
56. Nirantar SR, Yeo KS, Chee S et al (2013) A
generic scaffold for conversion of peptide
ligands into homogenous biosensors. Biosens
Bioelectron 47:421–428. doi:10.1016/j.
bios.2013.03.049
57. Huang J, Koide A, Makabe K, Koide S (2008)
Design of protein function leaps by directed
domain interface evolution. Proc Natl Acad
Sci U S A 105:6578–6583. doi:10.1073/
pnas.0801097105
58. Huang J, Koide S (2010) Rational conversion
of affinity reagents into label-free sensors for
peptide motifs by designed allostery. ACS
Chem Biol 5:273–277. doi:10.1021/
cb900284c
59. Huang J, Makabe K, Biancalana M et al
(2009) Structural basis for exquisite specificity
of affinity clamps, synthetic binding proteins
generated through directed domain-interface
evolution. J Mol Biol 392:1221–1231.
doi:10.1016/j.jmb.2009.07.067
60. Stein V, Alexandrov K (2014) Protease-based
synthetic sensing and signal amplification.
Proc Natl Acad Sci U S A 111:15934–15939.
doi:10.1073/pnas.1405220111
61. Zhang L, Lee KC, Bhojani MS et al (2007)
Molecular imaging of Akt kinase activity. Nat
Med 13:1114–1119. doi:10.1038/nm1608
62. Brun MA, Tan KT, Nakata E et al (2009)
Semisynthetic fluorescent sensor proteins
based on self-labeling protein tags. J Am
Chem Soc 131:5873–5884. doi:10.1021/
ja900149e
63. Schena A, Johnsson K (2014) Sensing acetylcholine and anticholinesterase compounds.
Angew Chem Int Ed Engl 53:1302–1305.
doi:10.1002/anie.201307754
64. Brun MA, Griss R, Reymond L et al (2011)
Semisynthesis of fluorescent metabolite sensors on cell surfaces. J Am Chem Soc
133:16235–16242. doi:10.1021/ja206915m
65. Brun MA, Tan KT, Griss R et al (2012) A
semisynthetic fluorescent sensor protein for
glutamate. J Am Chem Soc 134:7676–7678.
doi:10.1021/ja3002277
66. Griss R, Schena A, Reymond L et al (2014)
Bioluminescent sensor proteins for point-ofcare therapeutic drug monitoring. Nat
Chem Biol 10:598–603. doi:10.1038/
nchembio.1554
67. Xue L, Karpenko IA, Hiblot J, Johnsson K
(2015) Imaging and manipulating proteins in
live cells through covalent labeling. Nat Chem
Biol 11:1–7. doi:10.1038/nchembio.1959
68. Street AG, Mayo SL (1999) Computational
protein design. Structure 7(5):R105–R109.
doi:10.1016/S0969-2126(99)80062-8
69. Samish I, MacDermaid CM, Perez-Aguilar
JM, Saven JG (2011) Theoretical and computational protein design. Annu Rev Phys Chem
62:129–149.
doi:10.1146/
annurev-physchem-032210-103509
70. Khoury GA, Smadbeck J, Kieslich CA,
Floudas CA (2014) Protein folding and de
novo protein design for biotechnological
applications. Trends Biotechnol 32:99–109.
doi:10.1016/j.tibtech.2013.10.008
71. Kuhlman B, Dantas G, Ireton GC et al (2003)
Design of a novel globular protein fold with
atomic-level accuracy. Science 302:1364–
1368. doi:10.1126/science.1089427
72. Koga N, Tatsumi-Koga R, Liu G et al (2012)
Principles for designing ideal protein structures. Nature 491:222–227. doi:10.1038/
nature11600
Engineering Synthetic Protein Switches
48. Whitaker WR, Davis SA, Arkin AP, Dueber
JE (2012) Engineering robust control
of two- component system phosphotransfer
using modular scaffolds. Proc Natl Acad
Sci 109:18090–18095. doi:10.1073/pnas.
1209230109
49. Skerker JM, Perchuk BS, Siryaporn A et al
(2008) Rewiring the specificity of twocomponent signal transduction systems. Cell
133:1043–1054.
doi:10.1016/j.
cell.2008.04.040
50. Gasser C, Taiber S, Yeh C-M et al (2014)
Engineering of a red-light-activated human
cAMP/cGMP-specific
phosphodiesterase.
Proc Natl Acad Sci 111:8803–8808.
doi:10.1073/pnas.1321600111
51. Lai A, Sato PM, Peisajovich SG (2015)
Evolution of synthetic signaling scaffolds by
recombination of modular protein domains.
ACS Synth Biol 4:714–722. doi:10.1021/
sb5003482
52. Peisajovich SG, Garbarino JE, Wei P, Lim WA
(2010) Rapid diversification of cell signaling
phenotypes by modular domain recombination. Science 328:368–372. doi:10.1126/
science.1182376
53. Wend S, Wagner HJ, Müller K et al (2014)
Optogenetic control of protein kinase activity
in mammalian cells. ACS Synth Biol 3:280–
285. doi:10.1021/sb400090s
54. Wu YI, Frey D, Lungu OI et al (2009) A
genetically encoded photoactivatable Rac
controls the motility of living cells. Nature
461:104–108. doi:10.1038/nature08241
55. Levskaya A, Weiner OD, Lim WA, Voigt CA
(2009) sup: spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 461:997–1001. doi:10.1038/
nature08446
56. Nirantar SR, Yeo KS, Chee S et al (2013) A
generic scaffold for conversion of peptide
ligands into homogenous biosensors. Biosens
Bioelectron 47:421–428. doi:10.1016/j.
bios.2013.03.049
57. Huang J, Koide A, Makabe K, Koide S (2008)
Design of protein function leaps by directed
domain interface evolution. Proc Natl Acad
Sci U S A 105:6578–6583. doi:10.1073/
pnas.0801097105
58. Huang J, Koide S (2010) Rational conversion
of affinity reagents into label-free sensors for
peptide motifs by designed allostery. ACS
Chem Biol 5:273–277. doi:10.1021/
cb900284c
59. Huang J, Makabe K, Biancalana M et al
(2009) Structural basis for exquisite specificity
of affinity clamps, synthetic binding proteins
generated through directed domain-interface
evolution. J Mol Biol 392:1221–1231.
doi:10.1016/j.jmb.2009.07.067
60. Stein V, Alexandrov K (2014) Protease-based
synthetic sensing and signal amplification.
Proc Natl Acad Sci U S A 111:15934–15939.
doi:10.1073/pnas.1405220111
61. Zhang L, Lee KC, Bhojani MS et al (2007)
Molecular imaging of Akt kinase activity. Nat
Med 13:1114–1119. doi:10.1038/nm1608
62. Brun MA, Tan KT, Nakata E et al (2009)
Semisynthetic fluorescent sensor proteins
based on self-labeling protein tags. J Am
Chem Soc 131:5873–5884. doi:10.1021/
ja900149e
63. Schena A, Johnsson K (2014) Sensing acetylcholine and anticholinesterase compounds.
Angew Chem Int Ed Engl 53:1302–1305.
doi:10.1002/anie.201307754
64. Brun MA, Griss R, Reymond L et al (2011)
Semisynthesis of fluorescent metabolite sensors on cell surfaces. J Am Chem Soc
133:16235–16242. doi:10.1021/ja206915m
65. Brun MA, Tan KT, Griss R et al (2012) A
semisynthetic fluorescent sensor protein for
glutamate. J Am Chem Soc 134:7676–7678.
doi:10.1021/ja3002277
66. Griss R, Schena A, Reymond L et al (2014)
Bioluminescent sensor proteins for point-ofcare therapeutic drug monitoring. Nat
Chem Biol 10:598–603. doi:10.1038/
nchembio.1554
67. Xue L, Karpenko IA, Hiblot J, Johnsson K
(2015) Imaging and manipulating proteins in
live cells through covalent labeling. Nat Chem
Biol 11:1–7. doi:10.1038/nchembio.1959
68. Street AG, Mayo SL (1999) Computational
protein design. Structure 7(5):R105–R109.
doi:10.1016/S0969-2126(99)80062-8
69. Samish I, MacDermaid CM, Perez-Aguilar
JM, Saven JG (2011) Theoretical and computational protein design. Annu Rev Phys Chem
62:129–149.
doi:10.1146/
annurev-physchem-032210-103509
70. Khoury GA, Smadbeck J, Kieslich CA,
Floudas CA (2014) Protein folding and de
novo protein design for biotechnological
applications. Trends Biotechnol 32:99–109.
doi:10.1016/j.tibtech.2013.10.008
71. Kuhlman B, Dantas G, Ireton GC et al (2003)
Design of a novel globular protein fold with
atomic-level accuracy. Science 302:1364–
1368. doi:10.1126/science.1089427
72. Koga N, Tatsumi-Koga R, Liu G et al (2012)
Principles for designing ideal protein structures. Nature 491:222–227. doi:10.1038/
nature11600
Engineering Synthetic Protein Switches