of intrinsically disordered protein complexes
using NMR spectroscopy. Curr Opin Struct
Biol 54:10–18. https://doi.org/10.1016/j.
sbi.2018.09.007
8. Williams MA (2013) Protein–ligand interactions: fundamentals. In: Williams MA, Daviter
T (eds) Protein-ligand interactions. Humana
Press, Totowa, NJ, pp 3–34. https://doi.org/
10.1007/978-1-62703-398-5_1.
9. Martin SR, Schilstra MJ (2013) Rapid mixing
kinetic techniques. Methods Mol Biol
1008:119–138.
https://doi.org/10.1007/
978-1-62703-398-5_5
10. Bagshaw CR (2017) Biomolecular kinetics: a
step-by-step guide. CRC Press, Taylor & Francis Group, Boca Raton, FL
11. Gianni S, Jemth P (2017) How fast is proteinligand association? Trends Biochem Sci
42:847–849. https://doi.org/10.1016/j.tibs.
2017.08.007
12. Johnson CM (n.d.) Isothermal titration
calorimetry
13. Chemes LB, Sa ´nchez IE, de Prat-Gay G (2011)
Kinetic recognition of the retinoblastoma
tumor suppressor by a specific protein target.
J Mol Biol 412:267–284. https://doi.org/10.
1016/j.jmb.2011.07.015
14. Li-Blatter X, Zweifel L, Sharpe T (2020) A
familiar protein-ligand interaction revisited
with multiple methods. In: Protein-ligand
interactions. Wiley-VCH, Weinheim
15. Dosnon M, Bonetti D, Morrone A, Erales J, di
Silvio E, Longhi S, Gianni S (2015) Demonstration of a folding after binding mechanism in
the recognition between the measles virus
NTAIL and X domains. ACS Chem Biol
10:795–802.
https://doi.org/10.1021/
cb5008579
16. Dogan J, Schmidt T, Mu X, Engstro ¨m A ˚ ,
Jemth P (2012) Fast association and slow transitions in the interaction between two intrinsically disordered protein domains. J Biol Chem
287:34316–34324.
https://doi.org/10.
1074/jbc.M112.399436
17. Ou L, Matthews M, Pang X, Zhou H-X (2017)
The dock-and-coalesce mechanism for the
association of a WASP disordered region with
the Cdc42 GTPase. FEBS J 284:3381–3391.
https://doi.org/10.1111/febs.14197
18. Kuzmic P (2009) DynaFit--a software package
for
enzymology.
Methods
Enzymol
467:247–280.
https://doi.org/10.1016/
S0076-6879(09)67010-5
19. Johnson KA, Simpson ZB, Blom T (2009)
Global kinetic explorer: a new computer
program for dynamic simulation and fitting of
kinetic data. Anal Biochem 387:20–29.
https://doi.org/10.1016/j.ab.2008.12.024
20. Malatesta F (2005) The study of bimolecular
reactions under non-pseudo-first order conditions. Biophys Chem 116:251–256. https://
doi.org/10.1016/j.bpc.2005.04.006
21. A ˚ berg E, Karlsson OA, Andersson E, Jemth P
(2018) Binding kinetics of the intrinsically disordered p53 family transactivation domains
and MDM2. J Phys Chem B 122:6899–6905.
https://doi.org/10.1021/acs.jpcb.8b03876
22. Olson ST, Srinivasan KR, Bjo ¨rk I, Shore JD
(1981) Binding of high affinity heparin to antithrombin III. Stopped flow kinetic studies of
the binding interaction. J Biol Chem
256:11073–11079
23. Gianni S, Dogan J, Jemth P (2014) Distinguishing induced fit from conformational
selection. Biophys Chem 189C:33–39.
https://doi.org/10.1016/j.bpc.2014.03.003
24. Dogan J, Mu X, Engstro ¨m A ˚ , Jemth P (2013)
The transition state structure for coupled binding and folding of disordered protein domains.
Sci Rep 3:2076. https://doi.org/10.1038/
srep02076
25. Giri R, Morrone A, Toto A, Brunori M, Gianni
S (2013) Structure of the transition state for
the binding of c-Myb and KIX highlights an
unexpected order for a disordered system. Proc
Natl Acad Sci U S A 110:14942–14947.
https://doi.org/10.1073/pnas.1307337110
26. Rogers JM, Oleinikovas V, Shammas SL, Wong
CT, De Sancho D, Baker CM, Clarke J (2014)
Interplay between partner and ligand facilitates
the folding and binding of an intrinsically disordered protein. Proc Natl Acad Sci
111:15420–15425.
https://doi.org/10.
1073/pnas.1409122111
27. Dogan J, Jonasson J, Andersson E, Jemth P
(2015) Binding rate constants reveal distinct
features of disordered protein domains. Biochemistry 54:4741–4750. https://doi.org/
10.1021/acs.biochem.5b00520
28. Karlsson E, Andersson E, Dogan J, Gianni S,
Jemth P, Camilloni C (2019) A structurally
heterogeneous transition state underlies coupled binding and folding of disordered proteins. J Biol Chem 294:1230. https://doi.
org/10.1074/jbc.RA118.005854
29. Shoemaker BA, Portman JJ, Wolynes PG
(2000) Speeding molecular recognition by
using the folding funnel: the fly-casting mechanism. Proc Natl Acad Sci U S A
132
Elin Karlsson and Per Jemth
using NMR spectroscopy. Curr Opin Struct
Biol 54:10–18. https://doi.org/10.1016/j.
sbi.2018.09.007
8. Williams MA (2013) Protein–ligand interactions: fundamentals. In: Williams MA, Daviter
T (eds) Protein-ligand interactions. Humana
Press, Totowa, NJ, pp 3–34. https://doi.org/
10.1007/978-1-62703-398-5_1.
9. Martin SR, Schilstra MJ (2013) Rapid mixing
kinetic techniques. Methods Mol Biol
1008:119–138.
https://doi.org/10.1007/
978-1-62703-398-5_5
10. Bagshaw CR (2017) Biomolecular kinetics: a
step-by-step guide. CRC Press, Taylor & Francis Group, Boca Raton, FL
11. Gianni S, Jemth P (2017) How fast is proteinligand association? Trends Biochem Sci
42:847–849. https://doi.org/10.1016/j.tibs.
2017.08.007
12. Johnson CM (n.d.) Isothermal titration
calorimetry
13. Chemes LB, Sa ´nchez IE, de Prat-Gay G (2011)
Kinetic recognition of the retinoblastoma
tumor suppressor by a specific protein target.
J Mol Biol 412:267–284. https://doi.org/10.
1016/j.jmb.2011.07.015
14. Li-Blatter X, Zweifel L, Sharpe T (2020) A
familiar protein-ligand interaction revisited
with multiple methods. In: Protein-ligand
interactions. Wiley-VCH, Weinheim
15. Dosnon M, Bonetti D, Morrone A, Erales J, di
Silvio E, Longhi S, Gianni S (2015) Demonstration of a folding after binding mechanism in
the recognition between the measles virus
NTAIL and X domains. ACS Chem Biol
10:795–802.
https://doi.org/10.1021/
cb5008579
16. Dogan J, Schmidt T, Mu X, Engstro ¨m A ˚ ,
Jemth P (2012) Fast association and slow transitions in the interaction between two intrinsically disordered protein domains. J Biol Chem
287:34316–34324.
https://doi.org/10.
1074/jbc.M112.399436
17. Ou L, Matthews M, Pang X, Zhou H-X (2017)
The dock-and-coalesce mechanism for the
association of a WASP disordered region with
the Cdc42 GTPase. FEBS J 284:3381–3391.
https://doi.org/10.1111/febs.14197
18. Kuzmic P (2009) DynaFit--a software package
for
enzymology.
Methods
Enzymol
467:247–280.
https://doi.org/10.1016/
S0076-6879(09)67010-5
19. Johnson KA, Simpson ZB, Blom T (2009)
Global kinetic explorer: a new computer
program for dynamic simulation and fitting of
kinetic data. Anal Biochem 387:20–29.
https://doi.org/10.1016/j.ab.2008.12.024
20. Malatesta F (2005) The study of bimolecular
reactions under non-pseudo-first order conditions. Biophys Chem 116:251–256. https://
doi.org/10.1016/j.bpc.2005.04.006
21. A ˚ berg E, Karlsson OA, Andersson E, Jemth P
(2018) Binding kinetics of the intrinsically disordered p53 family transactivation domains
and MDM2. J Phys Chem B 122:6899–6905.
https://doi.org/10.1021/acs.jpcb.8b03876
22. Olson ST, Srinivasan KR, Bjo ¨rk I, Shore JD
(1981) Binding of high affinity heparin to antithrombin III. Stopped flow kinetic studies of
the binding interaction. J Biol Chem
256:11073–11079
23. Gianni S, Dogan J, Jemth P (2014) Distinguishing induced fit from conformational
selection. Biophys Chem 189C:33–39.
https://doi.org/10.1016/j.bpc.2014.03.003
24. Dogan J, Mu X, Engstro ¨m A ˚ , Jemth P (2013)
The transition state structure for coupled binding and folding of disordered protein domains.
Sci Rep 3:2076. https://doi.org/10.1038/
srep02076
25. Giri R, Morrone A, Toto A, Brunori M, Gianni
S (2013) Structure of the transition state for
the binding of c-Myb and KIX highlights an
unexpected order for a disordered system. Proc
Natl Acad Sci U S A 110:14942–14947.
https://doi.org/10.1073/pnas.1307337110
26. Rogers JM, Oleinikovas V, Shammas SL, Wong
CT, De Sancho D, Baker CM, Clarke J (2014)
Interplay between partner and ligand facilitates
the folding and binding of an intrinsically disordered protein. Proc Natl Acad Sci
111:15420–15425.
https://doi.org/10.
1073/pnas.1409122111
27. Dogan J, Jonasson J, Andersson E, Jemth P
(2015) Binding rate constants reveal distinct
features of disordered protein domains. Biochemistry 54:4741–4750. https://doi.org/
10.1021/acs.biochem.5b00520
28. Karlsson E, Andersson E, Dogan J, Gianni S,
Jemth P, Camilloni C (2019) A structurally
heterogeneous transition state underlies coupled binding and folding of disordered proteins. J Biol Chem 294:1230. https://doi.
org/10.1074/jbc.RA118.005854
29. Shoemaker BA, Portman JJ, Wolynes PG
(2000) Speeding molecular recognition by
using the folding funnel: the fly-casting mechanism. Proc Natl Acad Sci U S A
132
Elin Karlsson and Per Jemth