Folding and binding of an intrinsically disordered protein: Fast, but not 'diffusion-limited'

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Folding and binding of an intrinsically disordered protein : Fast, but not 'diffusion-limited'. / Rogers, Joseph M.; Steward, Annette; Clarke, Jane.

In: Journal of the American Chemical Society, Vol. 135, No. 4, 30.01.2013, p. 1415-1422.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rogers, JM, Steward, A & Clarke, J 2013, 'Folding and binding of an intrinsically disordered protein: Fast, but not 'diffusion-limited'', Journal of the American Chemical Society, vol. 135, no. 4, pp. 1415-1422. https://doi.org/10.1021/ja309527h

APA

Rogers, J. M., Steward, A., & Clarke, J. (2013). Folding and binding of an intrinsically disordered protein: Fast, but not 'diffusion-limited'. Journal of the American Chemical Society, 135(4), 1415-1422. https://doi.org/10.1021/ja309527h

Vancouver

Rogers JM, Steward A, Clarke J. Folding and binding of an intrinsically disordered protein: Fast, but not 'diffusion-limited'. Journal of the American Chemical Society. 2013 Jan 30;135(4):1415-1422. https://doi.org/10.1021/ja309527h

Author

Rogers, Joseph M. ; Steward, Annette ; Clarke, Jane. / Folding and binding of an intrinsically disordered protein : Fast, but not 'diffusion-limited'. In: Journal of the American Chemical Society. 2013 ; Vol. 135, No. 4. pp. 1415-1422.

Bibtex

@article{c9b50f764902488a8ef8f8f9217aec73,
title = "Folding and binding of an intrinsically disordered protein: Fast, but not 'diffusion-limited'",
abstract = "Coupled folding and binding of intrinsically disordered proteins (IDPs) is prevalent in biology. As the first step toward understanding the mechanism of binding, it is important to know if a reaction is 'diffusion-limited' as, if this speed limit is reached, the association must proceed through an induced fit mechanism. Here, we use a model system where the 'BH3 region' of PUMA, an IDP, forms a single, contiguous α-helix upon binding the folded protein Mcl-1. Using stopped-flow techniques, we systematically compare the rate constant for association (k+) under a number of solvent conditions and temperatures. We show that our system is not 'diffusion-limited', despite having a k+ in the often-quoted 'diffusion-limited' regime (10 5-106 M-1 s-1 at high ionic strength) and displaying an inverse dependence on solvent viscosity. These standard tests, developed for folded protein-protein interactions, are not appropriate for reactions where one protein is disordered.",
author = "Rogers, {Joseph M.} and Annette Steward and Jane Clarke",
year = "2013",
month = jan,
day = "30",
doi = "10.1021/ja309527h",
language = "English",
volume = "135",
pages = "1415--1422",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "ACS Publications",
number = "4",

}

RIS

TY - JOUR

T1 - Folding and binding of an intrinsically disordered protein

T2 - Fast, but not 'diffusion-limited'

AU - Rogers, Joseph M.

AU - Steward, Annette

AU - Clarke, Jane

PY - 2013/1/30

Y1 - 2013/1/30

N2 - Coupled folding and binding of intrinsically disordered proteins (IDPs) is prevalent in biology. As the first step toward understanding the mechanism of binding, it is important to know if a reaction is 'diffusion-limited' as, if this speed limit is reached, the association must proceed through an induced fit mechanism. Here, we use a model system where the 'BH3 region' of PUMA, an IDP, forms a single, contiguous α-helix upon binding the folded protein Mcl-1. Using stopped-flow techniques, we systematically compare the rate constant for association (k+) under a number of solvent conditions and temperatures. We show that our system is not 'diffusion-limited', despite having a k+ in the often-quoted 'diffusion-limited' regime (10 5-106 M-1 s-1 at high ionic strength) and displaying an inverse dependence on solvent viscosity. These standard tests, developed for folded protein-protein interactions, are not appropriate for reactions where one protein is disordered.

AB - Coupled folding and binding of intrinsically disordered proteins (IDPs) is prevalent in biology. As the first step toward understanding the mechanism of binding, it is important to know if a reaction is 'diffusion-limited' as, if this speed limit is reached, the association must proceed through an induced fit mechanism. Here, we use a model system where the 'BH3 region' of PUMA, an IDP, forms a single, contiguous α-helix upon binding the folded protein Mcl-1. Using stopped-flow techniques, we systematically compare the rate constant for association (k+) under a number of solvent conditions and temperatures. We show that our system is not 'diffusion-limited', despite having a k+ in the often-quoted 'diffusion-limited' regime (10 5-106 M-1 s-1 at high ionic strength) and displaying an inverse dependence on solvent viscosity. These standard tests, developed for folded protein-protein interactions, are not appropriate for reactions where one protein is disordered.

UR - http://www.scopus.com/inward/record.url?scp=84873828976&partnerID=8YFLogxK

U2 - 10.1021/ja309527h

DO - 10.1021/ja309527h

M3 - Journal article

C2 - 23301700

AN - SCOPUS:84873828976

VL - 135

SP - 1415

EP - 1422

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 4

ER -

ID: 244651199