20. Greenfield NJ (2006) Using circular dichroism
spectra to estimate protein secondary structure.
Nat Protoc 1:2876–2890. https://doi.org/
10.1038/nprot.2006.202
21. Greenfield NJ (2006) Determination of the
folding of proteins as a function of denaturants,
osmolytes or ligands using circular dichroism.
Nat Protoc 1:2733–2741. https://doi.org/
10.1038/nprot.2006.229
22. Rule GS, Hitchens TK (2006) Fundamentals
of protein NMR spectroscopy. Springer,
Dordrecht
23. Zerbe O, Jurt S (2014) Applied NMR spectroscopy for chemists and life scientists. WileyVCH, Weinheim
24. Gr€ aslund S et al (2008) Protein production and
purification. Nat Methods 5:135–146.
https://doi.org/10.1038/nmeth.f.202
25. Medrano G, Dolan MC, Condori J, Radin DN,
Cramer CL (2012) Quality assessment of
recombinant proteins produced in plants. In:
Lorence A (ed) Recombinant gene expression.
Humana Press, Totowa, NJ, pp 535–564
26. Dupeux F, Ro ¨wer M, Seroul G, Blot D, Ma ´rquez JA (2011) A thermal stability assay can
help to estimate the crystallization likelihood of
biological samples. Acta Crystallogr D Biol
Crystallogr 67:915–919. https://doi.org/10.
1107/S0907444911036225
27. Monsellier E, Bedouelle H (2005) Quantitative measurement of protein stability from
unfolding equilibria monitored with the fluorescence maximum wavelength. Protein Eng
Des Sel 18:445–456. https://doi.org/10.
1093/protein/gzi046
28. Moon CP, Fleming KG (2011) Using tryptophan fluorescence to measure the stability of
membrane proteins folded in liposomes. Methods Enzymol 492:189–211. https://doi.org/
10.1016/B978-0-12-381268-1.00018-5
29. Z ˇ olda ´k G, Jancura D, Sedla ´k E (2017) The
fluorescence intensities ratio is not a reliable
parameter for evaluation of protein unfolding
transitions. Protein Sci 26:1236–1239.
https://doi.org/10.1002/pro.3170
30. Pantoliano MW, Petrella EC, Kwasnoski JD,
Lobanov VS, Myslik J, Graf E, Carver T,
Asel E, Springer BA, Lane P, Salemme FR
(2001) High-density miniaturized thermal
shift assays as a general strategy for drug discovery. J Biomol Screen 6:429–440. https://
doi.org/10.1177/108705710100600609
31. Boivin S, Kozak S, Meijers R (2013) Optimization of protein purification and characterization using Thermofluor screens. Protein Expr
Purif 91:192–206. https://doi.org/10.1016/
j.pep.2013.08.002
32. Durowoju IB, Bhandal KS, Hu J, Carpick B,
Kirkitadze M (2017) Differential scanning calorimetry - a method for assessing the thermal
stability and conformation of protein antigen. J
Vis Exp (121):e55262. https://doi.org/10.
3791/55262
33. Quezada AG, Dı ´az-Salazar AJ, Cabrera N,
Pe ´rez-Montfort R, Pin ˜eiro A ´ , Costas M
(2017) Interplay between protein thermal flexibility and kinetic stability. Structure
25:167–179. https://doi.org/10.1016/j.str.
2016.11.018
34. Lebendiker M, Danieli T (2014) Production of
prone-to-aggregate proteins. FEBS Lett
588:236–246.
https://doi.org/10.1016/j.
febslet.2013.10.044
35. Jancarik J, Pufan R, Hong C, Kim SH, Kim R
(2004) Optimum solubility (OS) screening: an
efficient method to optimize buffer conditions
for homogeneity and crystallization of proteins. Acta Crystallogr D Biol Crystallogr
60:1670–1673.
https://doi.org/10.1107/
S0907444904010972
36. Wang J, Matayoshi E (2012) Solubility at the
molecular level: development of a critical
aggregation concentration (CAC) assay for
estimating compound monomer solubility.
Pharm Res 29:1745–1754. https://doi.org/
10.1007/s11095-012-0730-8
37. Le Maire M, Champeil P, Møller JV (2000)
Interaction of membrane proteins and lipids
with solubilizing detergents. Biochim Biophys
Acta
1508:86–111.
https://doi.org/10.
1016/S0304-4157(00)00010-1
38. Schuler MA, Denisov IG, Sligar SG (2013)
Nanodiscs as a new tool to examine lipid–protein interactions. In: Kleinschmidt JH
(ed) Lipid-protein interactions: methods and
protocols. Humana Press, Totowa, NJ, pp
415–433
39. Stroud Z, Hall SCL, Dafforn TR (2018) Purification of membrane proteins free from conventional detergents: SMA, new polymers, new
opportunities and new insights. Methods
147:106–117.
https://doi.org/10.1016/j.
ymeth.2018.03.011
40. Oluwole AO, Danielczak B, Meister A, Babalola JO, Vargas C, Keller S (2017) Solubilization of membrane proteins into functional
lipid-bilayer nanodiscs using a diisobutylene/
maleic acid copolymer. Angew Chem Int Ed
56:1919–1924.
https://doi.org/10.1002/
anie.201610778
41. Hardy D, Bill RM, Jawhari A, Rothnie AJ
(2016) Overcoming bottlenecks in the membrane protein structural biology pipeline. Biochem Soc Trans 44:838–844. https://doi.org/
10.1042/bst20160049
Protein Quality Control
45
spectra to estimate protein secondary structure.
Nat Protoc 1:2876–2890. https://doi.org/
10.1038/nprot.2006.202
21. Greenfield NJ (2006) Determination of the
folding of proteins as a function of denaturants,
osmolytes or ligands using circular dichroism.
Nat Protoc 1:2733–2741. https://doi.org/
10.1038/nprot.2006.229
22. Rule GS, Hitchens TK (2006) Fundamentals
of protein NMR spectroscopy. Springer,
Dordrecht
23. Zerbe O, Jurt S (2014) Applied NMR spectroscopy for chemists and life scientists. WileyVCH, Weinheim
24. Gr€ aslund S et al (2008) Protein production and
purification. Nat Methods 5:135–146.
https://doi.org/10.1038/nmeth.f.202
25. Medrano G, Dolan MC, Condori J, Radin DN,
Cramer CL (2012) Quality assessment of
recombinant proteins produced in plants. In:
Lorence A (ed) Recombinant gene expression.
Humana Press, Totowa, NJ, pp 535–564
26. Dupeux F, Ro ¨wer M, Seroul G, Blot D, Ma ´rquez JA (2011) A thermal stability assay can
help to estimate the crystallization likelihood of
biological samples. Acta Crystallogr D Biol
Crystallogr 67:915–919. https://doi.org/10.
1107/S0907444911036225
27. Monsellier E, Bedouelle H (2005) Quantitative measurement of protein stability from
unfolding equilibria monitored with the fluorescence maximum wavelength. Protein Eng
Des Sel 18:445–456. https://doi.org/10.
1093/protein/gzi046
28. Moon CP, Fleming KG (2011) Using tryptophan fluorescence to measure the stability of
membrane proteins folded in liposomes. Methods Enzymol 492:189–211. https://doi.org/
10.1016/B978-0-12-381268-1.00018-5
29. Z ˇ olda ´k G, Jancura D, Sedla ´k E (2017) The
fluorescence intensities ratio is not a reliable
parameter for evaluation of protein unfolding
transitions. Protein Sci 26:1236–1239.
https://doi.org/10.1002/pro.3170
30. Pantoliano MW, Petrella EC, Kwasnoski JD,
Lobanov VS, Myslik J, Graf E, Carver T,
Asel E, Springer BA, Lane P, Salemme FR
(2001) High-density miniaturized thermal
shift assays as a general strategy for drug discovery. J Biomol Screen 6:429–440. https://
doi.org/10.1177/108705710100600609
31. Boivin S, Kozak S, Meijers R (2013) Optimization of protein purification and characterization using Thermofluor screens. Protein Expr
Purif 91:192–206. https://doi.org/10.1016/
j.pep.2013.08.002
32. Durowoju IB, Bhandal KS, Hu J, Carpick B,
Kirkitadze M (2017) Differential scanning calorimetry - a method for assessing the thermal
stability and conformation of protein antigen. J
Vis Exp (121):e55262. https://doi.org/10.
3791/55262
33. Quezada AG, Dı ´az-Salazar AJ, Cabrera N,
Pe ´rez-Montfort R, Pin ˜eiro A ´ , Costas M
(2017) Interplay between protein thermal flexibility and kinetic stability. Structure
25:167–179. https://doi.org/10.1016/j.str.
2016.11.018
34. Lebendiker M, Danieli T (2014) Production of
prone-to-aggregate proteins. FEBS Lett
588:236–246.
https://doi.org/10.1016/j.
febslet.2013.10.044
35. Jancarik J, Pufan R, Hong C, Kim SH, Kim R
(2004) Optimum solubility (OS) screening: an
efficient method to optimize buffer conditions
for homogeneity and crystallization of proteins. Acta Crystallogr D Biol Crystallogr
60:1670–1673.
https://doi.org/10.1107/
S0907444904010972
36. Wang J, Matayoshi E (2012) Solubility at the
molecular level: development of a critical
aggregation concentration (CAC) assay for
estimating compound monomer solubility.
Pharm Res 29:1745–1754. https://doi.org/
10.1007/s11095-012-0730-8
37. Le Maire M, Champeil P, Møller JV (2000)
Interaction of membrane proteins and lipids
with solubilizing detergents. Biochim Biophys
Acta
1508:86–111.
https://doi.org/10.
1016/S0304-4157(00)00010-1
38. Schuler MA, Denisov IG, Sligar SG (2013)
Nanodiscs as a new tool to examine lipid–protein interactions. In: Kleinschmidt JH
(ed) Lipid-protein interactions: methods and
protocols. Humana Press, Totowa, NJ, pp
415–433
39. Stroud Z, Hall SCL, Dafforn TR (2018) Purification of membrane proteins free from conventional detergents: SMA, new polymers, new
opportunities and new insights. Methods
147:106–117.
https://doi.org/10.1016/j.
ymeth.2018.03.011
40. Oluwole AO, Danielczak B, Meister A, Babalola JO, Vargas C, Keller S (2017) Solubilization of membrane proteins into functional
lipid-bilayer nanodiscs using a diisobutylene/
maleic acid copolymer. Angew Chem Int Ed
56:1919–1924.
https://doi.org/10.1002/
anie.201610778
41. Hardy D, Bill RM, Jawhari A, Rothnie AJ
(2016) Overcoming bottlenecks in the membrane protein structural biology pipeline. Biochem Soc Trans 44:838–844. https://doi.org/
10.1042/bst20160049
Protein Quality Control
45